bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry
Authors: Isabelle Maxim , Moreel Xavier , Gagné Jean-Philippe , Rouleau Michèle , Ethier Chantal , Gagné Pierre , Hendzel Michael J , Poirier Guy G
Published: April 2010

Background

Poly(ADP-ribose) polymerases (PARPs) catalyze the formation of poly(ADP-ribose) (pADPr), a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose) glycohydrolase (PARG), on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosyl)ation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS) aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions.

Results

PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1.

Conclusions

This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose) metabolism.
Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout
Authors: Crespo Diego , Bonnet Emilie , Roher Nerea , MacKenzie Simon A , Krasnov Aleksei , Goetz Frederick W , Bobe Julien , Planas Josep V
Published: April 2010

Background

The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor alpha (TNF alpha) and other immune factors, are produced and act on the reproductive system. However, TNF alpha is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNF alpha in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta).

Methods

To determine the in vivo regulation of TNF alpha expression in the ovary, preovulatory brook trout (Salvelinus fontinalis) were injected intraperitoneally with either saline or bacterial lipopolysaccharide (LPS). In control and recombinant trout TNF alpha (rtTNF alpha)-treated brown trout granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI) staining. Furthermore, we determined the in vitro effects of rtTNF alpha on follicle contraction and testosterone production in preovulatory brown trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNF alpha-treated ovarian tissue by microarray and real-time PCR (qPCR) analyses.

Results

LPS administration in vivo causes a significant induction of the ovarian expression of TNF alpha. Treatment with rtTNF alpha induces granulosa cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNF alpha causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNF alpha induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. Furthermore, the expression of kallikrein, TOP-2, serine protease 23 and ADAM 22, genes that have been postulated to be involved in proteolytic and tissue remodeling processes during ovulation in trout, increases in follicles incubated in the presence of rtTNF alpha.

Conclusions

In view of these results, we propose that TNF alpha could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction.
Personal, social and environmental correlates of healthy weight status amongst mothers from socioeconomically disadvantaged neighborhoods: findings from the READI study
Authors: MacFarlane Abbie , Abbott Gavin , Crawford David , Ball Kylie
Published: April 2010

Background

Socioeconomically disadvantaged mothers are at high risk of obesity, yet the aetiology of obesity in this group remains poorly understood. The aim of this study was to examine the perceived personal, social and physical environmental factors associated with resilience to obesity among mothers from socioeconomically disadvantaged neighbourhoods.

Methods

Survey data were provided by a cohort of 1840 women aged 18-46 years with dependent children (aged 0-18 years) from 40 urban and 40 rural socioeconomically disadvantaged neighbourhoods across Victoria, Australia. Mothers responded to a number of questions relating to personal, social and environmental influences on their physical activity and eating habits. Mothers' weight status was classified as healthy weight (BMI: 18.5-24.99), overweight (BMI: 25-29.99) or obese (BMI: 30+).

Results

Mothers' weight status was bivariably associated with factors from all three domains (personal, social and physical environmental). In a multivariable model, mothers' perceived ability to make time for healthy eating (OR = 1.34) and physical activity (OR = 1.11) despite family commitments, and the frequency with which families ate healthy low-fat foods with mothers (OR = 1.28) remained significantly positively associated with healthy weight status. The frequency with which families encouraged eating healthy low-fat foods remained negatively associated (OR = 0.81) with weight status; ie greater encouragement was associated with less healthy weight status.

Conclusions

Drawing on the characteristics of mothers resilient to obesity might assist in developing intervention strategies to help other mothers in socioeconomically disadvantaged neighbourhoods to manage their weight. Such strategies might focus on planning for and prioritising time for healthy eating and physical activity behaviours, and including family members in and encouraging family mealtimes.
Immune mechanisms of protection: can adjuvants rise to the challenge?
Authors: McKee Amy S , MacLeod Megan KL , Kappler John W , Marrack Philippa
Published: April 2010

For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens.
The SURgical PAtient Safety System (SURPASS) checklist optimizes timing of antibiotic prophylaxis
Authors: de Vries Eefje N , Dijkstra Lucia , Smorenburg Susanne M , Meijer R Peter , Boermeester Marja A
Published: April 2010

Background

Surgical site infection (SSI) is an adverse event in which a close relation between process of care and outcome has been demonstrated: administration of antibiotic prophylaxis decreases the risk of SSI. In our tertiary referral centre, a SURgical PAtient Safety System (SURPASS) checklist was developed and implemented. This multidisciplinary checklist covers the entire surgical pathway and includes, among other items, administration of antibiotic prophylaxis before induction of anaesthesia. The aim of this study was to determine the effect of SURPASS implementation on timing of antibiotic prophylaxis.

Methods

A retrospective analysis was performed on two cohorts of patients: one cohort of surgical patients that underwent surgery before implementation of the checklist and a comparable cohort after implementation. The interval between administration of antibiotic prophylaxis and incision was compared between the two cohorts.

Results

A total of 772 surgical procedures were included. More than half of procedures were gastro-intestinal; others were vascular, trauma and hernia repair procedures. After implementation, the checklist was used in 81.4% of procedures. The interval between administration of antibiotic prophylaxis and incision increased from 23.9 minutes before implementation of SURPASS to 29.9 minutes after implementation (p = 0.047). In procedures where the checklist was used, the interval increased to 32.9 minutes (p = 0.004). The proportion of patients that did not receive antibiotics until after the incision decreased significantly.

Conclusion

The use of the SURPASS checklist leads to better compliance with regard to the timing of antibiotic prophylaxis administration.
Cold storage and cryopreservation of tick cell lines
Authors: Lallinger Gertrud , Zweygarth Erich , Bell-Sakyi Lesley , Passos Lygia MF
Published: April 2010

Background

Tick cell lines are now available from fifteen ixodid and argasid species of medical and veterinary importance. However, some tick cell lines can be difficult to cryopreserve, and improved protocols for short- and long-term low temperature storage will greatly enhance their use as tools in tick and tick-borne pathogen research. In the present study, different protocols were evaluated for cold storage and cryopreservation of tick cell lines derived from Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) microplus, Ixodes ricinus and Ixodes scapularis. For short-term cold storage, cells were kept under refrigeration at 6°C for 15, 30 and 45 days. For cryopreservation in liquid nitrogen, use of a sucrose-phosphate-glutamate freezing buffer (SPG) as cryoprotectant was compared with dimethylsulfoxide (DMSO) supplemented with sucrose. Cell viability was determined by the trypan blue exclusion test and cell morphology was evaluated in Giemsa-stained cytocentrifuge smears.

Results

Cold storage at 6°C for up to 30 days was successful in preserving R. (B.) microplus, R. (B.) decoloratus, I. ricinus and I. scapularis cell lines; lines from the latter three species could be easily re-cultivated after 45 days under refrigeration. While cell lines from all four tick species cryopreserved with 6% DMSO were successfully resuscitated, the R. (B.) decoloratus cells did not survive freezing in SPG and of the other three species, only the R. (B.) microplus cells resumed growth during the observation period.

Conclusions

This constitutes the first report on successful short-term refrigeration of cells derived from R. (B.) decoloratus, R. (B.) microplus, and I. ricinus, and use of SPG as an alternative to DMSO for cryopreservation, thus making an important contribution to more reliable and convenient tick cell culture maintenance.
Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action
Authors: Hillenmeyer Maureen E , Ericson Elke , Davis Ronald W , Nislow Corey , Koller Daphne , Giaever Guri
Published: April 2010

We systematically analyzed the relationships between gene fitness profiles (co-fitness) and drug inhibition profiles (co-inhibition) from several hundred chemogenomic screens in yeast. Co-fitness predicted gene functions distinct from those derived from other assays and identified conditionally dependent protein complexes. Co-inhibitory compounds were weakly correlated by structure and therapeutic class. We developed an algorithm predicting protein targets of chemical compounds and verified its accuracy with experimental testing. Fitness data provide a novel, systems-level perspective on the cell.
Human uterine epithelial cell secretions regulate dendritic cell differentiation and responses to TLR ligands
Authors: Ochiel Daniel O , Ghosh Mimi , Fahey John V , Guyre Paul M , Wira Charles R
Published: April 2010

Immune mediators secreted by human uterine epithelial cells confer tolerogenic properties to dendritic cells.

The balance between immunity and tolerance in the endometrium is governed by dynamic interactions of UEC and immune cells including DC. In this study, we tested the hypothesis that soluble immune mediators secreted by UEC modulate the differentiation and functions of human DC. We found that DC differentiated with CM from polarized UEC (i.e., CM-DC) expressed significantly lower surface CD86. Upon activation with LPS or PIC, the expression of CD80, CD86, and CD83 was decreased significantly on CM-DC relative to Con-DC. Further, mRNA for TLR3, TLR4, and TLR5 was decreased significantly in CM-DC relative to Con-DC. As a functional read-out of the effect of CM on DC, we determined the following parameters: First, analysis of cytokine production showed that when compared with Con-DC, CM-DC responded to LPS or PIC stimulation with enhanced IL-10 production but undetectable IL-12p70 secretion. Second, RT-PCR analysis showed that CM-DC significantly expressed higher mRNA for IDO, an immune tolerance-promoting enzyme. Lastly, in a MLR assay, CM-DC induced significantly lower allogeneic proliferative responses compared with Con-DC. These findings indicate collectively that epithelial cells confer a tolerogenic phenotype to DC in the endometrium. Our results suggest novel cellular and molecular mechanisms for the regulation of adaptive immunity within the FRT.
Depth migration by the Gaussian beam summation method
Authors: Popov Mikhail M. , Semtchenok Nikolay M. , Popov Peter M. , Verdel Arie R.
Published: April 2010

Seismic depth migration aims to produce an image of seismic reflection interfaces. Ray methods are suitable for subsurface target-oriented imaging and are less costly compared to two-way wave-equation-based migration, but break down in cases when a complex velocity structure gives rise to the appearance of caustics. Ray methods also have difficulties in correctly handling the different branches of the wavefront that result from wave propagation through a caustic. On the other hand, migration methods based on the two-way wave equation, referred to as reverse-time migration, are known to be capable of dealing with these problems. However, they are very expensive, especially in the 3D case. It can be prohibitive if many iterations are needed, such as for velocity-model building. Our method relies on the calculation of the Green functions for the classical wave equation by per-forming a summation of Gaussian beams for the direct and back-propagated wavefields. The subsurface image is obtained by cal-culating the coherence between the direct and backpropagated wavefields. To a large extent, our method combines the advantages of the high computational speed of ray-based migration with the high accuracy of reverse-time wave-equation migration because it can overcome problems with caustics, handle all arrivals, yield good images of steep flanks, and is readily extendible to target-oriented implementation. We have demonstrated the quality of our method with several state-of-the-art benchmark subsurface models, which have velocity variations up to a high degree of complexity. Our algorithm is especially suited for efficient imaging of selected subsurface subdomains, which is a large advantage particularly for 3D imaging and velocity-model refinement applications such as subsalt velocity-model improvement. Because our method is also capable of providing highly accurate migration results in structurally complex subsurface settings, we have also included the concept of true-amplitude imaging in our migration technique.
Phase III Trial Comparing Adjuvant Treatment With Pegylated Interferon Alfa-2b Versus Observation: Prognostic Significance of Autoantibodies—EORTC 18991
Authors: Bouwhuis Marna G. , Suciu Stefan , Testori Alessandro , Kruit Wim H. , Salès François , Patel Poulam , Punt Cornelis J. , Santinami Mario , Spatz Alain , ten Hagen Timo L.M. , Eggermont Alexander M.M.
Published: April 2010

Purpose

Conflicting data have been reported concerning the prognostic value of autoimmune antibodies in patients with melanoma treated with adjuvant interferon alfa-2b (IFN). We evaluated the prognostic significance of autoantibodies in the European Organisation for Research and Treatment of Cancer 18991 trial, comparing long-term administration of pegylated IFN (PEG-IFN) with observation.

Patients and Methods

Anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined by enzyme-linked immunosorbent assays in 296 patients before random assignment and every 6 months after random assignment for up to 5 years. Prognostic impact of autoantibodies on recurrence-free survival (RFS) was assessed using the following three Cox models: a model that considered autoantibody appearance as a time-independent variable (model 1); a model that considered a patient to be autoantibody positive from the first positive test (model 2); and a model in which the most recent autoantibody test was used to define the status of the patient (model 3).

Results

Patients who were autoantibody negative at baseline were analyzed (n = 220). Occurrence of autoantibodies during follow-up was higher in the PEG-IFN–treated patients (18% in the observation arm v 52% in the PEG-IFN arm). Autoantibody appearance was of prognostic importance by using model 1 (hazard ratio [HR] = 0.56; 95% CI, 0.36 to 0.87; P = .01). However, when guarantee-time bias was taken into account using model 2 (HR = 1.19; 95% CI, 0.75 to 1.88; P = .46) or method 3 (HR = 1.14; 95% CI, 0.71 to 1.83; P = .59), significance was lost. Results were similar when treatment groups were analyzed separately.

Conclusion

Appearance of autoimmune antibodies is neither a prognostic nor a predictive factor for improved outcome in patients with melanoma treated with PEG-IFN.
Long-Term Outcome in Children With Relapsed Acute Lymphoblastic Leukemia After Time-Point and Site-of-Relapse Stratification and Intensified Short-Course Multidrug Chemotherapy: Results of Trial ALL-REZ BFM 90
Authors: Tallen Gesche , Ratei Richard , Mann Georg , Kaspers Gertjan , Niggli Felix , Karachunsky Alexandr , Ebell Wolfram , Escherich Gabriele , Schrappe Martin , Klingebiel Thomas , Fengler Ruediger , Henze Günter , von Stackelberg Arend
Published: April 2010

Purpose

The multicenter trial ALL-REZ BFM (ie, Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster) 90 was designed to improve prognosis for children with relapsed acute lymphoblastic leukemia (ALL) by time-to-relapse– and site-of-relapse–adapted stratification and by introduction of novel chemotherapy elements and to evaluate new prognostic parameters in a large, population-based cohort.

Patients and Methods

Five hundred twenty-five patients stratified into risk groups A (early bone marrow [BM] relapses), B (late BM relapses), and C (isolated extramedullary relapses) received alternating short-course intensive polychemotherapy (in blocks R1, R2, or R3) and cranial/craniospinal irradiation followed by maintenance therapy. Block R3 (high-dose cytarabine and etoposide) was introduced to improve the outcome compared with historical controls. Patients with early BM or T-ALL relapse (poor prognosis group [PPG]) were eligible for experimental regimens. One hundred seventeen patients received stem-cell transplantation (SCT).

Results

The probabilities (and standard deviations) of event-free survival (pEFS) and overall survival (pOS) at 10 years were 0.30 ± .02 and 0.36 ± .02, respectively. Significant differences existed between strategic groups (pEFSA = .17 ± .03; pEFSB = .43 ± .04; pEFSC = .54 ± .06; pEFSPPG = .15 ± .03; log-rank P < .001). Patients of high-risk groups A plus PPG did better with SCT than with chemotherapy (pEFS = .33 ± .05 v 0.20 ± .05; P = .005). The pEFS was similar to trials ALL-REZ BFM 85/87 (.36 ± .03. v 0.37 ± .03; P = .419; PPG excluded). Time point, site of relapse, immunophenotype, and SCT were significant predictors of pEFS in multivariate analyses.

Conclusion

More than one third of patients in this large, population-based trial were cured. Neither R3 nor adaptation of chemotherapy intensity was capable of improving pEFS or of overcoming prognostic factors. In high-risk patients, remission induction regimens must be improved, and allogeneic SCT should be recommended in patients achieving second complete remission.
Acute Myeloid Leukemia or Myelodysplastic Syndrome in Randomized Controlled Clinical Trials of Cancer Chemotherapy With Granulocyte Colony-Stimulating Factor: A Systematic Review
Authors: Lyman Gary H. , Dale David C. , Wolff Debra A. , Culakova Eva , Poniewierski Marek S. , Kuderer Nicole M. , Crawford Jeffrey
Published: April 2010

Purpose

To evaluate the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and overall mortality in patients receiving chemotherapy with or without granulocyte colony-stimulating factor (G-CSF), a systematic review of randomized controlled trials (RCTs) was conducted.

Methods

Electronic databases searched through October 2008 identified 3,794 articles for initial screening. Eligibility included solid tumor or lymphoma patients randomly assigned to chemotherapy with or without G-CSF support, ≥ 2 years of follow-up, and reporting AML/MDS or all second malignancies. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk (AR) estimates ± 95% CIs were calculated by the Mantel-Haenszel method.

Results

In the 25 eligible RCTs, 6,058 and 6,746 patients were randomly assigned to receive chemotherapy with and without initial G-CSF support, respectively. At mean and median follow-up across studies of 60 and 53 months, respectively, AML/MDS was reported in 22 control patients and 43 G-CSF–treated patients, with an estimated RR of 1.92 (95% CI, 1.19 to 3.07; P = .007) and AR increase of 0.41% (95% CI, 0.10% to 0.72%; P = .009). Deaths were reported in 1,845 patients randomly assigned to G-CSF and in 2,099 controls, for estimates of RR and AR decrease of 0.897 (95% CI, 0.857 to 0.938; P < .001) and 3.40% (95% CI, 2.01% to 4.80%; P < .001), respectively. Greater RR reduction for mortality was seen for both larger studies (P = .05) and greater chemotherapy dose-intensity (P = .012).

Conclusion

Delivered chemotherapy dose-intensity and risk of AML/MDS are increased but all-cause mortality is decreased in patients receiving chemotherapy with G-CSF support. Greater reductions in mortality were observed with greater chemotherapy dose-intensity.
Adherence Is the Critical Factor for Achieving Molecular Responses in Patients With Chronic Myeloid Leukemia Who Achieve Complete Cytogenetic Responses on Imatinib
Authors: Marin David , Bazeos Alexandra , Mahon Francois-Xavier , Eliasson Lina , Milojkovic Dragana , Bua Marco , Apperley Jane F. , Szydlo Richard , Desai Ritti , Kozlowski Kasia , Paliompeis Christos , Latham Victoria , Foroni Letizia , Molimard Mathieu , Reid Alistair , Rezvani Katy , de Lavallade Hugues , Guallar Cristina , Goldman John , Khorashad Jamshid S.
Published: April 2010

Purpose

There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence.

Methods

Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed.

Results

Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence ≤ 90%; in 12 of these patients (14%), adherence was ≤ 80%. There was a strong correlation between adherence rate (≤ 90% or > 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response [MMR]) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk [RR], 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was ≤ 80% (P < .001). Patients whose imatinib doses were increased had poor adherence (86.4%). In this latter population, adherence was the only independent predictor for inability to achieve an MMR (RR, 17.66; P = .006).

Conclusion

In patients with CML treated with imatinib for some years, poor adherence may be the predominant reason for inability to obtain adequate molecular responses.
European Development of Clofarabine as Treatment for Older Patients With Acute Myeloid Leukemia Considered Unsuitable for Intensive Chemotherapy
Authors: Burnett Alan K. , Russell Nigel H. , Kell Jonathan , Dennis Michael , Milligan Donald , Paolini Stefania , Yin John , Culligan Dominic , Johnston Peter , Murphy John , McMullin Mary-Frances , Hunter Ann , Das-Gupta Emma , Clark Richard , Carr Robert , Hills Robert K.
Published: April 2010

Purpose

Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.

Patients and Methods

Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were ≥ 65 years of age and deemed unsuitable for intensive chemotherapy.

Results

A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score ≥ 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival.

Conclusion

Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.
Divining Zoroastro: Masonic Elements in Handel's Orlando
Authors: Gibbons William
Published: April 2010

The magician Zoroastro plays a critical role in Handel's opera Orlando (1733). He opens the first act with a dramatic monologue, keeps the hero Orlando from wreaking too much havoc in his madness, and eventually brings the opera to a peaceful conclusion. Despite his importance to the plot, however, Zoroastro was a late addition to the libretto, created expressly for Handel's production—an addition calculated to appeal to London audiences. The image of Zoroaster (the obvious model for Zoroastro) was prevalent in London during the 1720s and 1730s, appearing prominently in popular literary works of the time, and was particularly associated with Freemasonry. Using Zoroastro/Zoroaster as a starting point, this article reveals the presence Masonic imagery and ideology in Orlando, and suggests that Handel and his librettist were tailoring their operas to the wealthy Masonic-friendly opera audiences of 1730s.
Health Care Reform and Federalism
Authors: Greer Scott L. , Jacobson Peter D.
Published: April 2010

Health policy debates are replete with discussions of federalism, most often when advocates of reform put their hopes in states. But health policy literature is remarkably silent on the question of allocation of authority, rarely asking which levels of government ought to lead. We draw on the larger literatures about federalism, found mostly in political science and law, to develop a set of criteria for allocating health policy authority between states and the federal government. They are social justice, procedural democracy, compatibility with value pluralism, institutional capability, and economic sustainability. Of them, only procedural democracy and compatibility with value pluralism point to state leadership. In examining these criteria, we conclude that American policy debates often get federalism backward, putting the burden of health care coverage policy on states that cannot enact or sustain it, while increasing the federal role in issues where the arguments for state leadership are compelling. We suggest that the federal government should lead present and future financing of health care coverage, since it would require major changes in American intergovernmental relations to make innovative state health care financing sustainable outside a strong federal framework.
Prudential Concealment in Shi`ite Islam
Authors: Sachedina Abdulaziz
Published: April 2010

The paper undertakes to investigate the Shī`ī practice of prudential concealment (taqīya) as a source of both quietism and political activism. The practice functioned as a strategy of survival for the Shī `ī minority living under hostile Sunni regimes. Although Sunni ulema criticized the practice as dissimulation and, hence, morally wrong, ironically they too adopted the strategy when encountering autocratic and oppressive Sunni regimes that suffocated the right of the people to voice their demand for just treatment. The article demonstrates that the strategy created a specific sphere of existence for the Shī `ites, known as the “abode of prudential concealment,” which incrementally allowed Muslim opposition to engage in underground activity for regime change and for a political transformation of the public order that accorded with Islamic ideals. In light of Muslim political theology providing doctrinal resources for Muslim societies to work toward the common good in the public sphere, this latter space functions as a means of critical evaluation of the existing autocratic governments in the Muslim world, prompting political action, however underground. The major conclusion of the paper is that although the practice was developed by the Shī `ī minority living under intolerable political conditions, at different times under unbearable political conditions and the absence of democratic processes, it has provided Muslims a strategy to regroup and engage in political transformation.
The Cat and the Camel
Authors: Mulhall Stephen
Published: April 2010

This response to “Morality or Moralism?” by Émilie Hache and Bruno Latour, while accepting the plausibility and importance of their critique of moralism in the name of morality, identifies a number of questionable steps and assumptions in their development of it. Mulhall's response questions an ambiguity in their specifications of what morality and moralism are—an unexplained tendency on their part to occlude distinctively nonhuman animal life in favor of the inanimate when advocating a concern for the nonhuman, and what appears to be a misreading of Michel Serres.
How Reliable Is Moral Sensitivity?
Authors: Zamir Tzachi
Published: April 2010

This response to “Morality or Moralism?” by Emilie Hache and Bruno Latour takes issue with their distinction between two kinds of morality. Hache and Latour see a difference between morality as sensitivity and morality as principled claims regarding moral considerability. They then argue for form-content contradiction/harmony between these purportedly opposing senses. In responding, Zamir argues that these operations can be construed as distinct kinds of sensitivity. Arguments that advocate bringing nonhuman animals into moral consideration can be abstract and general. But this does not mean that such arguments or those who make them are insensitive. Some kinds of sensitivity are attuned to general facts rather than to particulars. Hache and Latour thus err by reducing moral sensitivity to a response to particulars, which leads them to perceive form-content tensions where these do not exist. Zamir's response also argues against a tendency in posthumanist animal ethics—a tendency shared by Hache and Latour's article—to refuse descending to discuss the actual practical questions regarding animals that Anglo-American animal ethics explores. Zamir examines (and rejects) some possible posthumanist arguments that might support remaining philosophically uninvolved in these discussions.
Mechanical control of tissue and organ development
Authors: Mammoto Tadanori , Ingber Donald E.
Published: April 2010

Many genes and molecules that drive tissue patterning during organogenesis and tissue regeneration have been discovered. Yet, we still lack a full understanding of how these chemical cues induce the formation of living tissues with their unique shapes and material properties. Here, we review work based on the convergence of physics, engineering and biology that suggests that mechanical forces generated by living cells are as crucial as genes and chemical signals for the control of embryological development, morphogenesis and tissue patterning.
A Comprehensive Numerical Stress—Strain Analysis of Laser Beam Butt-Welded Titanium Compared with Austenitic Steel Joints
Authors: Casavola C , Lamberti L , Pappalettere C , Tattoli F
Published: April 2010

Experimental tests on laser beam butt-welded joints made of commercially pure titanium and Ti—6Al—4V alloy showed a fatigue behaviour quite different from that usually observed in the case of AISI 304 joints connected with the same welding technique. In fact, fatigue failures of titanium joints were observed at the level of the base material but not in the notch region, as have been found for austenitic steel. In order to explain this experimental evidence, very detailed finite element models are developed in this paper. The models reproduce the real cord profiles of Ti—6Al—4V and AISI 304 steel welded joints detected by a high-precision coordinate measuring machine. Furthermore, mechanical properties given as input to the finite element models correspond to the real joint microstructure revealed by micro-hardness tests carried out in the different regions of the specimen. Finally, finite element models reproduce the distribution of porosity detected via microscopic inspection of the fractured surfaces. Interactions of weld geometry, material properties, presence/absence of porosity, and level of applied stress are considered in this study, which includes nine different finite element models of titanium and austenitic steel joints. A relevant complication in the analysis of titanium joints is represented by the small thickness and stress concentration effects.

Numerical results show that the stress field in titanium joints is sensitive to the combined effect of weld seam geometry and presence of welding defects (pores). The latter produces stress concentration much more severe than that caused by the weld cord. Microstructural support length evaluated near the pores of titanium joints is about the same as that computed near the notch of austenitic steel joints (i.e. near 0). Furthermore, the Topper parameter evaluated for the titanium joints in the presence of pores is much smaller than for the stainless steel joints. Microstructure modifications must be accounted for in order to assess correctly the fatigue behaviour of austenitic steel joints.
A Coupling Solution for Interfacial Stresses in a Plated Beam
Authors: Hao S-W , Li Y-Y , Sun J , Liu Q , Wang B , Yang H-Z
Published: April 2010

This paper presents a coupling solution for determining the elastic interfacial shear and normal stresses of a plated beam. The mismatch of the curvatures in the beam and plate is considered. This leads to the coupling of governing differential equations for the interfacial shear stresses and normal stresses. Existing solutions assume the beam and plate have an equal curvature to uncouple this effect. In this paper, however, it is shown that the mismatch of curvatures leads to a larger interfacial shear stress but a lower normal stress. The unequal curvatures resulting from the elastic deformation of the adhesive layer will have an obvious contribution to the bending moment distribution on beam and plate, especially when the flexural rigidity of the bonded plate increases: the vertical deformation of the adhesive layer near the end of plate will become larger and then results in an increasing contribution by interfacial stresses. These findings are therefore very important to the design of strengthened beams.
A Novel Method for Determining the Time and Location of Abrupt Fracture Initiation in Bones
Authors: Juszczyk M , Cristofolini L , Kaniuk J , Schileo E , Viceconti M
Published: April 2010

Investigation of bone failure is extremely important in orthopaedic biomechanics to reduce the risk of fracture in diseased and operated patients. Identification of the point where fracture starts would be extremely valuable to better understand bone mechanics. However, as abrupt fractures of bones occur in milliseconds, most in vitro studies report the failure load, but cannot localize the point of fracture initiation. Commercially available grid-based or foil crack gauges cannot be applied to the complex double-curvature geometry of bones. In this paper a method is proposed for preparing a fine conductive crack-grid on the bone surface, combined with a dedicated data logger. The proposed system offers a spatial resolution of 0.5—2.0 mm, and a sampling rate of 700 kHz. Suitability of the crack-grid to withstand bone strains prior to failure was checked. A preliminary application on bone specimens confirmed that: (a) preparation of the crack-grid on the bone surface is possible; (b) accurate and consistent results are obtained that enable identification of the fracture initiation point; (c) this method is sensitive to differences in crack propagation rate, depending on alignment with respect to the tissue structure, and on quality of the bone tissue. The applicability and accuracy of this method was finally shown on a real femur, which was tested while a high-speed camera and the proposed crack-grid simultaneously recorded abrupt fracture. The proposed system will provide new insights into fracture mechanics of bone structures (including abrupt fractures).
Passive Contra-Magnetized Parallel-Airgap Serial Flux Magnetic Bearings
Authors: Kalita K , Khoo W K S , Garvey S D , Hill-Cottingham R J , Rodger D , Eastham J F
Published: April 2010

Conventional magnetic bearings accomplish a specific load capacity, defined as the ratio of maximum sustainable weight to the total self-weight, of up to 35:1. In this paper, the authors introduce a class of passive magnetic bearings that comprise a large number of parallel airgaps and discs and can deliver specific load capacities substantially higher than 35:1. Two-dimensional planar, two-dimensional axi-symmetric, and three-dimensional finite-element analysis (FEA) have been undertaken to predict the force capability of the bearings. An unoptimized prototype passive magnetic bearing is constructed to demonstrate the concept and its force-carrying capacity. The experimental results are then compared with those obtained from the FEA. Further optimization of the bearings is done across the whole design space comprising tens of thousands of models using an automatic mesh generator in conjunction with solving the FE models in nested loops.
Experimental Study on Deformation and Shock Damage of Cylindrical Shell Structures Subjected to Underwater Explosion
Authors: Li L-J , Jiang W-K , Ai Y-H
Published: April 2010

The security evaluation of some structures shocked by an underwater explosion (UNDEX) frequently plays a key role in some cases, and it is necessary to accurately predict the damage condition of the structure in an UNDEX environment. This study investigates the dynamic linear and non-linear responses and shock damages of two kinds of submerged cylindrical shell models exposed to underwater spherical trinitrotoluene (TNT) charge explosions in a circular lake. Two endplates and a middle plate are mounted on the cylindrical shells to provide support and to create two enclosed spaces. The two kinds of cylindrical shell models with the same geometry characteristics are unfilled and main hull sand-filled. Fifteen different tests are carried out by changing the TNT explosive weights of 1 and 2 kg, standoff distances ranging from 3 to 0.3 m, and two explosion positions. Measured experimental results are compared with each other, and some transformed data are obtained. A detailed discussion on experimental results shows that the dynamic responses and damage modes are much different, and the main hull sand-filled cylindrical shell is more difficult to be damaged by the shock wave loading than the unfilled model. Edge cracks are mainly observed at the instrument hull of the main hull sand-filled model, but surface tearing and cracks are observed on both the main hull and the instrumental hull of the unfilled model, respectively.
The Biomechanical Effects of Variation in the Maximum Forces Exerted by Trunk Muscles on the Joint Forces and Moments in the Lumbar Spine: A Finite Element Analysis
Authors: Kim K , Lee S-K , Kim Y H
Published: April 2010

The weakening of trunk muscles is known to be related to a reduction of the stabilization function provided by the muscles to the lumbar spine; therefore, strengthening deep muscles might reduce the possibility of injury and pain in the lumbar spine. In this study, the effect of variation in maximum forces of trunk muscles on the joint forces and moments in the lumbar spine was investigated. Accordingly, a three-dimensional finite element model of the lumbar spine that included the trunk muscles was used in this study. The variation in maximum forces of specific muscle groups was then modelled, and joint compressive and shear forces, as well as resultant joint moments, which were presumed to be related to spinal stabilization from a mechanical viewpoint, were analysed. The increase in resultant joint moments occurred owing to decrease in maximum forces of the multifidus, interspinales, intertransversarii, rotatores, iliocostalis, longissimus, psoas, and quadratus lumborum. In addition, joint shear forces and resultant joint moments were reduced as the maximum forces of deep muscles were increased. These results from finite element analysis indicate that the variation in maximum forces exerted by trunk muscles could affect the joint forces and joint moments in the lumbar spine.
An accurate and efficient control over the present numerical model of depth of sputtering in focused ion beam milling
Authors: Bhavsar S N , Aravindan S , Venkateswara Rao P
Published: April 2010

In many applications, such as fabrication of microtools, microsurgical instruments, microgears, and so on, material must be removed precisely with a focused ion beam (FIB) milling process to generate a specified geometry on substrate material. A mathematical model is available to calculate depth of sputtering at each point on substrate material in order to generate a specified geometry, but the results of the existing model deviates from experimental data. In the current paper, normalized pixel spacing and ratio of redeposition to beam velocity are the two parameters that have been considered in calculation of depth of sputtering during the FIB milling process. A proposed mathematical model incorporating the effect of redeposition has been simulated for parabolic and rectangular trench profiles, and it has been proven to be better than the existing model through comparison with experimental data of parabolic and rectangular geometry on silicon material. In addition, efforts have been made to reduce the amount of numerical calculation in the simulation process by utilizing a Gaussian mask in the existing model instead of the usual Gaussian intensity function. The Gaussian mask prevents the need for repeated calculation of Gaussian intensity function in the mathematical model of depth of sputtering, and in turn reduces the time of computation.
Zinc disc implantation model of urinary bladder calculi and humane endpoints
Authors: Singh P K , Patil C R , Harlalka G V , Gaud N P
Published: April 2010

The zinc disc implantation-induced urinary bladder calculi model in the rat is commonly used for preclinical evaluation of the antiurolithiatic activity of test compounds. Certain published reports state that relatively long durations for which zinc discs must be implanted in the bladders of rats. Hence, there is a need to refine this model. These investigations aimed to determine whether long-term studies using the zinc disc implantation model provide any additional data that affect the final outcomes of the study. In this study, we evaluated the effects of a well-known antiurolithiatic polyherbal drug, Cystone, for different treatment durations of 10, 20 and 48 days postimplantation. Our results indicate that even the shortest duration of 10 days is sufficient to reveal antiurolithiatic effects of a test drug. Hence, in the zinc disc implantation-induced urinary bladder calculi model, the study duration is proposed to be minimized so as to reduce the distress caused to the rats due to long-term exposure to the implant. Further, it is suggested that the growth of the bladder calculi can be monitored by taking X-ray radiographs of the bladder deposits to decide the time to terminate the study. Use of preformed calcium oxalate crystal instead of zinc discs, as suggested in earlier reports by others, may also be considered to avoid the sacrifice of rats at the end of the study.
ASP, The Art and Science of Practice: In Search of the √N + 1 Rule
Authors: Rudisill J. Frank
Published: April 2010

In over 25 years of consulting in operations research, management science, quality management, and statistics, I have come across several rules of thumb that practitioners use frequently, but incorrectly. One is the “square root of (N) + 1” rule used in sampling and inspecting raw materials and finished goods. This paper describes several of my encounters with this rule and the circumstances of its use. I discuss how I used a nested design experiment to demonstrate to users that the rule was not appropriate for their situations. The paper also includes a “top 10” list of other rules of thumb and beliefs that people often use incorrectly. I offer tips that have helped me avoid these rules.