bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Xenopus laevisintestine reveal biological pathways underlying vertebrate gut adaptation from embryo to adult
Authors: Heimeier Rachel A , Das Biswajit , Buchholz Daniel R , Fiorentino Maria , Shi Yun-Bo
Published: May 2010

Background

To adapt to its changing dietary environment, the digestive tract is extensively remodeled from the embryo to the adult during vertebrate development. Xenopus laevis metamorphosis is an excellent model system for studying mammalian gastrointestinal development and is used to determine the genes and signaling programs essential for intestinal development and maturation.

Results

The metamorphosing intestine can be divided into four distinct developmental time points and these were analyzed with X. laevis microarrays. Due to the high level of conservation in developmental signaling programs and homology to mammalian genes, annotations and bioinformatics analysis were based on human orthologs. Clustering of the expression patterns revealed co-expressed genes involved in essential cell processes such as apoptosis and proliferation. The two largest clusters of genes have expression peaks and troughs at the climax of metamorphosis, respectively. Novel conserved gene ontology categories regulated during this period include transcriptional activity, signal transduction, and metabolic processes. Additionally, we identified larval/embryo- and adult-specific genes. Detailed analysis revealed 17 larval specific genes that may represent molecular markers for human colonic cancers, while many adult specific genes are associated with dietary enzymes.

Conclusions

This global developmental expression study provides the first detailed molecular description of intestinal remodeling and maturation during postembryonic development, which should help improve our understanding of intestinal organogenesis and human diseases. This study significantly contributes towards our understanding of the dynamics of molecular regulation during development and tissue renewal, which is important for future basic and clinical research and for medicinal applications.
Toll-like receptor signaling: a potential link among rheumatoid arthritis, systemic lupus, and atherosclerosis
Authors: Huang QiQuan , Pope Richard M
Published: May 2010

Review examines the potential role of signaling by endogenous TLR ligands in the pathogenesis of autoimmune disease and atherosclerosis and explores how they might be related.
Plastic yielding as a frequency and amplitude independent mechanism of seismic wave attenuation
Authors: Yarushina Victoria M. , Podladchikov Yuri Y.
Published: May 2010

We have developed a mathematical formulation of two mechanisms of compressional wave attenuation, which can occur within the solid rock frame prestressed up to its yield stress in part of its volume. Energy losses are attributed to two distinct processes: irreversible plastic yielding and formation of radial microfractures around microscopic cavities. Small-amplitude waves propagating through the rocks prestressed at their yield point would cause nonelastic strain to avoid building local stresses above the yield limit and attenuate some fraction of their energy per every loading cycle. New mechanisms of microscale yielding and microfracturing give rise to frequency-independent attenuation due to rate-independence of plasticity formulation. Quality factor [Formula: see text] predicted by the model is independent of strain amplitude for small strains and decreases with increasing amplitude for large strains. We found that attenuation can be high even for small seismic strains [Formula: see text]. Thus, [Formula: see text] is achieved at effective pressures greater than twice the yield strength of the solid matrix for the plastic yielding mechanism and at overpressures exceeding half tensile strength for microfracturing.
Phase III Multicenter Trial of Doxorubicin Plus Cyclophosphamide Followed by Paclitaxel Compared With Doxorubicin Plus Paclitaxel Followed by Weekly Paclitaxel As Adjuvant Therapy for Women With High-Risk Breast Cancer
Authors: Loesch David , Greco F. Anthony , Senzer Neil N. , Burris Howard A. , Hainsworth John D. , Jones Stephen , Vukelja Svetislava J. , Sandbach John , Holmes Frankie , Sedlacek Scot , Pippen John , Lindquist Deborah , McIntyre Kristi , Blum Joanne L. , Modiano Manuel R. , Boehm Kristi A. , Zhan Feng , Asmar Lina , Robert Nicholas
Published: May 2010

Purpose

This study compared disease-free survival (DFS) obtained with two different regimens of adjuvant therapy in high-risk breast cancer.

Methods

Women (who had performance status [PS] of 0 to 1) with operable, histologically confirmed, stage I to III adenocarcinoma of the breast were eligible. Patients had undergone primary surgery with no residual tumor. Treatments were as follows: arm 1 was doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks for four cycles followed by paclitaxel 175 mg/m2 every 3 weeks for four cycles (ie, AC-P); and arm 2 was doxorubicin 50 mg/m2 plus paclitaxel 200 mg/m2 every 3 weeks for four cycles followed by paclitaxel 80 mg/m2 weekly for 12 weeks.

Results

Overall, 1,830 patients were enrolled and 1,801 were treated: arm 1 (n = 906; AC→P) and arm 2 (n = 895; AP-WP). Overall, patients had a PS of 0 (88%), had estrogen receptor and progesterone receptor–positive disease (52%), had one to three positive nodes (46%), and were postmenopausal (57%); the median age was 52 years. Currently, 1,640 patients (90%) are alive. The 6-year DFS was 79% to 80% in both groups. Disease relapse was the cause of death for 83 patients in arm 1 and in 66 patients of arm 2. Overall 6-year survival rates were 82% and 87% in arms 1 and 2, respectively. Reasons for patients being taken off study treatment included toxicity (13% in arm 1 v 20% in arm 2), progressive disease or recurrence (7% v 5%), and consent withdrawn (9% v 8%), respectively. The most frequent toxicities were hematologic, including neutropenia and leukopenia followed by neuropathy, myalgia, nausea, fatigue, headache, arthralgia, and vomiting.

Conclusion

The results indicate that the AP-WP regimen is an equally effective and tolerable option for the adjuvant treatment of patients with high-risk breast cancer. The substitution of paclitaxel for cyclophosphamide results in comparable effectiveness of the regimen.
Phase I and Pharmacologic Study of SNS-032, a Potent and Selective Cdk2, 7, and 9 Inhibitor, in Patients With Advanced Chronic Lymphocytic Leukemia and Multiple Myeloma
Authors: Tong Wei-Gang , Chen Rong , Plunkett William , Siegel David , Sinha Rajni , Harvey R. Donald , Badros Ashraf Z. , Popplewell Leslie , Coutre Steven , Fox Judith A. , Mahadocon Kristi , Chen Tianling , Kegley Peggy , Hoch Ute , Wierda William G.
Published: May 2010

Purpose

SNS-032 is a highly selective and potent inhibitor of cyclin-dependent kinases (Cdks) 2, 7, and 9, with in vitro growth inhibitory effects and ability to induce apoptosis in malignant B cells. A phase I dose-escalation study of SNS-032 was conducted to evaluate safety, pharmacokinetics, biomarkers of mechanism-based pharmacodynamic (PD) activity, and clinical efficacy.

Patients and Methods

Parallel cohorts of previously treated patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) received SNS-032 as a loading dose followed by 6-hour infusion weekly for 3 weeks of each 4-week course.

Results

There were 19 patients with CLL and 18 with MM treated. Tumor lysis syndrome was the dose-limiting toxicity (DLT) for CLL, the maximum-tolerated dose (MTD) was 75 mg/m2, and the most frequent grade 3 to 4 toxicity was myelosuppression. One patient with CLL had more than 50% reduction in measurable disease without improvement in hematologic parameters. Another patient with low tumor burden had stable disease for four courses. For patients with MM, no DLT was observed and MTD was not identified at up to 75 mg/m2, owing to early study closure. Two patients with MM had stable disease and one had normalization of spleen size with treatment. Biomarker analyses demonstrated mechanism-based PD activity with inhibition of Cdk7 and Cdk9, decreases in Mcl-1 and XIAP expression level, and associated CLL cell apoptosis.

Conclusion

SNS-032 demonstrated mechanism-based target modulation and limited clinical activity in heavily pretreated patients with CLL and MM. Further single-agent, PD-based, dose and schedule modification is warranted to maximize clinical efficacy.
Lack of Efficacy of Bevacizumab Plus Irinotecan in Children With Recurrent Malignant Glioma and Diffuse Brainstem Glioma: A Pediatric Brain Tumor Consortium Study
Authors: Gururangan Sridharan , Chi Susan N. , Young Poussaint Tina , Onar-Thomas Arzu , Gilbertson Richard J. , Vajapeyam Sridhar , Friedman Henry S. , Packer Roger J. , Rood Brian N. , Boyett James M. , Kun Larry E.
Published: May 2010

Purpose

A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent malignant glioma (MG) and intrinsic brainstem glioma (BSG).

Patients and Methods

Eligible patients received two doses of BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ plus CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion weighted and T1 dynamic contrast–enhanced permeability imaging, BVZ pharmacokinetics, and estimation of vascular endothelial growth factor receptor 2 (VEGFR-2) phosphorylation in peripheral blood mononuclear cells (PBMC) after single-agent BVZ.

Results

Thirty-one evaluable patients received a median of two courses of BVZ plus CPT-11 (range, 1 to 19). No sustained responses were observed in either stratum. Median time to progression for all 34 eligible patients enrolled was 127 days for MG and 71 days for BSG. Progression-free survival rates at 6 months were 41.8% and 9.7% for MG and BSG, respectively. Toxicities related to BVZ included grade 1 to 3 fatigue in seven patients, grade 1 to 2 hypertension in seven patients, grade 1 CNS hemorrhage in four patients, and grade 4 CNS ischemia in two patients. The mean diffusion ratio decreased after two doses of BVZ in patients with MG only. Vascular permeability parameters did not change significantly after therapy in either stratum. Inhibition of VEGFR-2 phosphorylation in PBMC was detected in eight of 11 patients after BVZ exposure.

Conclusion

BVZ plus CPT-11 was well-tolerated but had minimal efficacy in children with recurrent malignant glioma and brainstem glioma.
Insulin Stimulates Human Skeletal Muscle Protein Synthesis via an Indirect Mechanism Involving Endothelial-Dependent Vasodilation and Mammalian Target of Rapamycin Complex 1 Signaling
Authors: Timmerman Kyle L. , Lee Jessica L. , Dreyer Hans C. , Dhanani Shaheen , Glynn Erin L. , Fry Christopher S. , Drummond Micah J. , Sheffield-Moore Melinda , Rasmussen Blake B. , Volpi Elena
Published: May 2010

Objective: Our objective was to determine whether endothelial-dependent vasodilation is an essential mechanism by which insulin stimulates human skeletal muscle protein synthesis and anabolism.

Subjects: Subjects were healthy young adults (n = 14) aged 31 ± 2 yr.

Design: Subjects were studied at baseline and during local leg infusion of insulin alone (control, n = 7) or insulin plus the nitric oxide synthase inhibitor NG-monomethyl-l-arginine (l-NMMA, n = 7) to prevent insulin-induced vasodilation.

Methods: We measured skeletal muscle protein metabolism with stable isotope tracers, blood flow with indocyanine green, capillary recruitment with contrast enhanced ultrasound, glucose metabolism with stable isotope tracers, and phosphorylation of proteins associated with insulin (Akt) and amino acid-induced mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling (mTOR, S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1) with Western blot analysis.

Results: No basal differences between groups were detected. During insulin infusion, blood flow and capillary recruitment increased in the control (P < 0.05) group only; Akt phosphorylation and glucose uptake increased in both groups (P < 0.05), with no group differences; and mTORC1 signaling increased more in control (P < 0.05) than in l-NMMA. Phenylalanine net balance increased (P < 0.05) in both groups, but with opposite mechanisms: increased protein synthesis (basal, 0.051 ± 0.006 %/h; insulin, 0.077 ± 0.008 %/h; P < 0.05) with no change in proteolysis in control and decreased proteolysis (P < 0.05) with no change in synthesis (basal, 0.061 ± 0.004 %/h; insulin, 0.050 ± 0.006 %/h; P value not significant) in l-NMMA.

Conclusions: Endothelial-dependent vasodilation and the consequent increase in nutritive flow and mTORC1 signaling, rather than Akt signaling, are fundamental mechanisms by which insulin stimulates muscle protein synthesis in humans. Additionally, these data underscore that insulin modulates skeletal muscle proteolysis according to its effects on nutritive flow.
Age and the Thyrotropin Response to Hypothyroxinemia
Authors: Over Rebecca , Mannan Sonia , Nsouli-Maktabi Hala , Burman Kenneth D. , Jonklaas Jacqueline
Published: May 2010

Context: Some studies suggest altered pituitary functioning and TSH production with aging.

Objective: Our objective was to test the hypothesis that less TSH production occurs despite comparable hypothyroxinemia with advancing age.

Design: We retrospectively studied adult outpatients of all ages with confirmed hypothyroidism and documented their TSH and free T4 concentrations.

Participants: Two populations of 112 patients were subdivided into four age groups: 1) patients newly diagnosed with primary hypothyroidism and 2) thyroid cancer patients undergoing l-T4 withdrawal in preparation for diagnostic or therapeutic radioiodine.

Main Outcome Measure: The relationship between paired free T4 and TSH concentrations and patient age was studied.

Results: With spontaneous hypothyroidism, the mean TSH concentration decreased nonsignificantly in each ascending age group with comparable free T4 (FT4) concentrations (<35 yr, 69 mIU/liter; 35–49 yr, 49 mIU/liter; 50–64 yr, 43 mIU/liter; >64 yr, 29 mIU/liter). With iatrogenic hypothyroidism, the mean TSH concentration decreased significantly in each ascending age group (<35 yr, 156 mIU/liter; 35–49 yr, 115 mIU/liter; 50–64 yr, 74 mIU/liter; >64 yr, 46 mIU/liter; P < 0.001) despite similar FT4 concentrations. The relationship between the log-transformed TSH and FT4 was significantly and inversely affected by age in multivariate analyses in both spontaneous hypothyroidism (P = 0.0005) and in iatrogenic hypothyroidism (P < 0.0001).

Conclusions: Age modifies the pituitary set point or response to comparably reduced free T4 concentrations, resulting in lesser serum TSH elevation in older individuals. This phenomenon occurs with both spontaneous and iatrogenic hypothyroidism. This may be an adaptive response in normal aging or a pathological alteration of pituitary function with age.
The Nature and Scope of the Us-Eu Relationship
Authors: Kaskarelis Vassilis
Published: May 2010

United by common values and threat perceptions, the United States and the EU are each other's natural allies and most obvious and important political and trade partners. Despite occasional misunderstandings, mainly on tactics, there are very few areas in which European and American interests and objectives do not coincide. It must be noted that Europe needs to be more effective internally and in its dealings with the United States. Nevertheless, past experience teaches the United States that this irreplaceable relationship will continue to develop not from more formalistic machinery or rigid definitions of burden-sharing but from sustained and results-oriented coordination, depending on the issue.
Weighing Macedonia's Entry into NATO
Authors: Siegel Scott N.
Published: May 2010

Greece's veto of the entry of the Former Yugoslav Republic of Macedonia (FYROM) into the North Atlantic Treaty Organization (NATO) in 2009 provides an opportunity to evaluate the possible costs and benefits of a FYROM membership. For NATO, FYROM's inclusion has only a marginal impact on the success of NATO's military missions. In fact, the inclusion of FYROM could mean more, not fewer, security challenges for the alliance. For FYROM, the benefits of NATO candidacy have not materialized. While its civil-military relations have improved, shortcomings still exist among FYROM's democratic and free-market institutions. Evaluating FYROM's case for membership results in a better understanding of the challenges and concerns related to continued eastward expansion.
Politics at Home, Politics in the World: The Return of the Political in Turkish Foreign Policy
Authors: Aktay Yasin
Published: May 2010

The “political” has been absent from Turkish foreign policy because the main difficulties facing the country were considered almost constitutive elements of Turkish national existence, so that they are kept incurable. This essay includes a brief history of the absence of the political in Turkish foreign policy. Some conservative and dogmatic considerations of limits in political life have been typical obstacles to change. When politicians address the obstacles, they threaten many economic and political interests. A radically different, recent approach in Turkey promotes political action to achieve “zero problems with the neighbors.” While we could previously see the removal of the political from foreign policy in Turkey, now we also can see the clear return of the political.
Playing the Eu: The Logic of Mythmaking in Bulgaria's Foreign Policy toward Central Asia
Authors: Kavalski Emilian
Published: May 2010

This essay examines the domestic logic informing the creation of Bulgaria's foreign policy. It contextualizes inferences made from Bulgaria's diplomatic attempt to “play the EU” during the visit by the Bulgarian minister of foreign affairs to Central Asia in September 2007. Inferences of the national narratives of Bulgaria's international involvement are contextualized to suggest that domestically the Europeanization of Bulgarian foreign policy has been preoccupied with negotiating the conflict between state and nation. A report on Central Asia indicates that the logic of mythmaking informs the domestic articulation of the foreign policy stance coming from Sofia, Bulgaria's capital, not only toward neighboring countries (where it might be expected, as has been well documented) but also toward regions that are not geographically proximate. Inferences are contextualized by the national narratives of Bulgaria's international involvement. Such positions suggest that domestically the Europeanization of Bulgarian foreign policy has been preoccupied with negotiating conflict between state and nation.
In the Queer Archive
Authors: Rohy Valerie
Published: May 2010

This essay examines figures of archives in Alison's Bechdel's 2006 memoir Fun Home—the museum-like family house, the father's home library, Alison's childhood diary, and the public libraries she frequented as a young adult—as occasions for reimagining the queer potentiality of historical narrative. While the memoir begins with a schematic distinction between fact and falsehood, nature and artifice, later chapters revise that view, in part by identifying within the queer archive the counterhistorical impulse Derrida calls archive fever. Informed by that ceaseless drive, Fun Home provides an opportunity to investigate the archive's relation to identity and history.
MAINSTREAM Fiction, GAY Reviewers, AND GAY MALE CULTURAL POLITICS IN THE 1970s
Authors: Distelberg Brian J.
Published: May 2010

An analysis of gay male reviewers' responses to major commercial publishers' expanded offerings of fiction by and about gay people during the 1970s reveals how reviewers constructed a machinery of gay-identified criticism, negotiated new definitions of gay identity, and forged a community of gay intellectuals and authors intent on using their own mainstream success to make evident to all the creativity and value of contemporary gay life. By decade's end, this gay literary elite had developed ideas about gay cultural politics and the proper relationship between activism and commercial cultural production that differed distinctly from those of gay political organizations and other gay activists. These developments sketch a richer and more complicated story of the evolution of gay identity and gay politics—particularly the politics of visibility—after Stonewall.
Moving Pictures
Authors: Sendziuk Paul , Hallas Roger , Hubbard Jim , Levine Debra
Published: May 2010

In the age of AIDS, film and video became one of the principal means for grief-stricken activists and artists to bear witness and make sense of the epidemic and the loss of their lovers and friends. This Moving Image Review comprises short texts that provide an overview of the films and videos that were produced and that have subsequently been appropriated and reworked by contemporary filmmakers for a variety of purposes. In re-viewing these works from a distance, the authors revise old assumptions about the nature of these films and videos and the people and the activist movement that they depict. Roger Hallas provides a counterpoint to this examination by acknowledging the importance of the film “archive” created by less recognizable independent and experimental queer filmmakers. Jim Hubbard, seeking to articulate the different strategies and aesthetic of AIDS activist video as opposed to film, finds some surprising similarities. Debra Levine, reviewing preserved tapes of ACT UP demonstrations and placing these alongside the more recently produced ACT UP oral history videos, concludes that participants in the demonstrations were driven by a compulsion to demonstrate kindness and care toward their fellow ACT UP members as much as they were motivated by anger (as their acts are commonly interpreted). And Paul Sendziuk offers a reassessment of Philadelphia, Hollywood's first big-budget film to address the topic of AIDS and homosexuality, arguing for the need to understand the historical circumstance of its production and its intended mainstream audience.
Why Men Still Aren't Enough
Authors: Watt Diane
Published: May 2010

In 1993 Speculum, the journal of the Medieval Academy of America, published a special issue titled “Studying Women: Sex, Gender, Feminism.” It was a milestone in medieval studies, marking, belatedly, institutional recognition of the important contribution feminism and gender studies had made to transforming scholarly understanding of medieval culture over the previous two decades. Within the special issue, one contribution was by a man: Allen J. Frantzen's provocatively titled “When Women Aren't Enough,” in which Frantzen charted the shift from the “women in history” approach to the rise of gender studies, arguing that, following what he saw as the triumph of feminism, “the study of the `masculine' has become as crucial as the study of the `feminine.'” More than fifteen years later, the debates have moved on, the terminology and theoretical frameworks have changed, and the victories of feminism seem short-lived. The major developments of the past two decades that have transformed our understanding of medieval culture and society have been the growth of the history of sexuality as a (sub)discipline in its own right and the impact of queer theory on literary criticism. As Frantzen predicted so accurately, the study of men and masculinity has been central to these new movements. However, in this essay reviewing four contributions to the field, I argue that women and femininity have once again become sidelined. Increasingly the terminology of both the history of sexuality and queer theory has become gender exclusive: homosexuality has come to mean, in common academic usage, male homosexuality; gay history is gay male history; queer sexualities are all-too-often queer male sexualities. Women are not given equal weight to men, and the histories of male and female sexualities are still artificially separated.
Diversity, Dissent, and Decision Making: The Challenge to Lgbt Politics
Authors: Stone Amy L.
Published: May 2010

Queer and radical criticisms of the LGBT movement have existed since the movement's origins. Indeed, within any movement there are tensions between radicalism and liberalism, assimilation and separatism, and the role of professional or hierarchical organizations. Examining three recent publications on the LGBT movement, I argue that within the LGBT movement there is a tension between queer radicalism and professionalism (which is often conflated with homonormativity and assimilation.) As the national LGBT movement grew, it inevitably developed professional, formal organizations. Although a necessity in maintaining movement coherence and focus, professional organizations are also deeply problematic because of how they suppress dissent and radicalism. Professional organizations also incorporate corporate diversity culture, which is often staffed and led by white professionals and targets only visible and fundable identities such as race and gender.
Redefining Identity Through Language in the Literature of the Diaspora
Authors: Bassiouney Reem
Published: May 2010

This essay examines the use of language in the literature that discusses the diaspora, with concentration on one novel. The essay concentrates on the diglossic situation that prevails in the Arab world, in which there are two varieties, high and a low, each with a different function. The high variety in the Arab world is modern standard Arabic, and the low variety is the different vernaculars of different countries. The question posed is whether the novel analyzed reflects realistic linguistic choices in the parts of the protagonists or whether this literature projects a different reality with different rules and language choices. If the latter case is true, then language may be used as a tool to redefine reality and project different identities. The choice of standard or vernacular will in fact have a discourse function as well as a creative one.
Collective methods of propulsion and steering for untethered microscale nanorobots navigating in the human vascular network
Authors: Martel S
Published: May 2010

In the field of medical nanorobotics, nanometre-scale components and phenomena are exploited within the context of robotics to provide new medical diagnostic and interventional procedures, or at least to enhance the existing ones. The best route for such miniature robots to access various regions inside the human body is certainly the vascular network. Such a network is made of nearly 100 000 km of blood vessels varying in diameters from a few millimetres in the arteries down to ∼ 4 μm in the capillaries with respective important variations in blood flow velocities. When injected in the blood circulatory network using existing modern techniques such as catheterization, such robots must travel from larger-diameter vessels before reaching much tinier capillaries. As such, the use of a single type of microscale robots capable of travelling in various environments and conditions related to such different blood vessels while being trackable by an external system seems, at the present time, inconceivable. Therefore, as explained in this article, an approach based on the use of several types of microscale robots with complementary methods of propulsion and steering capable of operating in a collective manner is more likely to achieve better results. This is especially true for interventions such as direct tumour targeting where the tiniest blood vessels such as the ones found in the angiogenesis network must be travelled.
Optimum Design of Local Cam Profile of a Valve Train
Authors: Qin W J , He J Q
Published: May 2010

In this paper, optimization of the local cam profile of a valve train modelled by a parameterized Bezier curve is described. Dynamic responses of the valve train are simulated through its multi-body system dynamics model built using ADAMS software. The kriging method is used to build the surrogate model, which presents the relationship between dynamic responses resulting from the multi-body system dynamics simulation and the parameters of the local Bezier profile. The local cam profile is optimized through a generic algorithm, such that the acceleration peak at the valve open phase is reduced significantly.
Superposition Buckling Analysis of Rectangular Plates Composed of Functionally Graded Materials Subjected to Non-Uniform Distributed In-Plane Loading
Authors: Najafizadeh M M , Mahdavian M , Khazaeinejad P
Published: May 2010

In this research, mechanical buckling of rectangular plates of functionally graded materials (FGMs) is considered. Equilibrium and stability equations of an FGM rectangular plate under uniform in-plane compression are derived. For isotropic materials, convergent buckling loads have been presented for non-uniformly compressed rectangular plates based on a rigorous superposition Fourier solution for the in-plane Airy stress field and Galerkin's approach for stability analysis. Results for isotropic cases are compared with reference articles and finite-element method solution. Finally, the results are achieved for a sample of FGM as well as the research on the effect of power law index on buckling loads.
Designing and testing a hydraulic inerter
Authors: Wang F-C , Hong M-F , Lin T-C
Published: May 2010

This article proposes a novel hydraulic inerter and experimentally verifies its properties. The inerter is a true two-terminal mechanical network element, which was invented to substitute for the mass in mechanical/electrical analogies. Previously, inerter concepts have been realized by rack-and-pinion and ball-screw devices. This article introduces a new hydraulic inerter device in which the forces are translated by hydraulic means. The dynamics of the device is discussed and experimentally verified. On the basis of the results, the proposed hydraulic inerter is shown to be effective.
Fuel mixing effect on the flickering of jet diffusion flames
Authors: Li J , Zhang Y
Published: May 2010

An experimental study has been performed for a buoyant jet diffusion flame, which was observed to oscillate at different frequencies spatially. The flame dynamics and structure were visualized by a commercial digital camera and a high-speed camera. Mixed fuel of methane and propane at certain proportion was found to generate very different vortex shedding behaviours. As a result, the flickering frequency of a methane/propane 1:1 mixture can be half of that of typically observed for pure methane or propane flame. The distance between adjacent flame puffs or the size of vortical structures in the reacting flow field, which can be modified by the fuel composition, was identified to be the key factor that affects the flickering frequencies. Repeated tests confirmed that mixed fuel at certain proportions can have a significant effect on the flame flickering frequency through the modification of vortex structure and dynamics.
The Effects of Train Brake Delay Time on In-Train Forces
Authors: Nasr A , Mohammadi S
Published: May 2010

In long trains, the braking signal from locomotive control valve takes a few seconds to reach the end cars. As a result, there is a time delay in the braking of the neighbouring cars (locomotives and wagons). This causes the running of rear cars into front cars, thus producing large forces in the buffers and couplers. The induced compression and tensile forces are mainly of longitudinal nature and considered to be responsible for large amount of expenses regarding rolling stock and track repairs as well as deterioration of safety operation of the trains. The effects of the train brake delay time on longitudinal dynamic behaviour of the freight trains are investigated in this article using simulation method. The freight trains considered are those currently operating in Iranian railways. The simulations are carried out for three different cases of long, medium, and short brake application delay times. For each case, three different train forward velocities are considered. The computed results presented here include in-train compression and tensile forces. Different modes of longitudinal dynamic interactions along the train length are also observed by simulations. The results are compared in order to give some new insight into the effect of train braking delay time on train longitudinal dynamics during braking.
A Study of a Numerical Analysis Method for the Wheel-Rail Wear of a Heavy-Haul Train
Authors: Chang C , Wang C , Chen B , Li L
Published: May 2010

The wheel-rail rolling contact finite-element model based on arbitrary Lagrangian-Eulerian finite-element method (FEM) is developed and applied to the wheel-rail steady-state rolling contact analysis. Based on the wheel-rail steady-state rolling contact analysis, the wheel profile wear prediction methodology is developed and applied to wear of the wheel flange and rail gauge corner when the heavy-haul train passes on sharp curve track. The vehicle dynamic model is built in the ADAMS software, and the forces of the axle boxes acquired from the vehicle system dynamic model are loaded on the model of three-dimensional non-linear finite-element steady-state analysis for wheelset rolling contact process. Steady-state rolling contact analysis based on three-dimensional non-linear finite element is solved by the ABAQUS software. In the FEM simulation, a material model with bilinear kinematic hardening property is used. The wear modelling is based on the Archard's wear model. Laplacian smoothing with area weights is used to smooth the meshes of wheel and rail. Finally, the simulation results of a heavy-haul train wheel are analysed.
Geometry and stiffness optimization for switches and crossings, and simulation of material degradation
Authors: Nicklisch D , Kassa E , Nielsen J , Ekh M , Iwnicki S
Published: May 2010

A methodology for simulating wear, rolling contact fatigue, and plastic deformation for a mixed traffic situation in switches and crossings (S&C) has been developed. The methodology includes simulation of dynamic vehicle—track interaction considering stochastic variations in input data, simulation of wheel—rail contacts accounting for non-linear material properties and plasticity, and simulation of wear and plastic deformation in the rail during the life of the S&C component. To find means of improving the switch panel design, the geometry of a designed track gauge variation in the switch panel has been represented in a parametric way. For traffic in the facing and trailing moves of the through route, an optimum solution was identified and then validated by evaluating a wide set of simulation cases (using different wheel profiles). The optimum design includes a 12 mm maximum gauge widening. Several crossing geometries were investigated to find an optimal geometric design for the crossing nose and wing rails. The MaKüDe design showed the best performance for moderately worn wheel profiles in both running directions (facing and trailing moves). In connection with reduced support stiffness (e.g. elastic rail pads), this crossing design is predicted to lead to a significant reduction of impact loads and consequently provide a high potential of life-cycle cost reduction.
Results to Exemplify the Joint EU Project INNOTRACK — Innovative Track Systems
Authors: Paulsson B , Ekberg A
Published: May 2010

The INNOTRACK - Innovative Track Systems research and development project was formally closed on 31 December 2009. The outcome of the project is summarized in some 140 deliverables. The research in INNOTRACK focuses on mixed traffic and deals with three key parts of the track, namely track support structure, switches and crossings, and rails and welding. The innovative results from INNOTRACK are, in addition to the technical analysis, scrutinized from a life-cycle cost and a reliability, availability, maintainability, and safety perspective as well as from a logistic standpoint. The results show that significant cost reductions are possible to reach. The article gives a short overview of INNOTRACK and then goes into more detail on some results with bearing on heavy haul operations.
An Inspection of Railway Ballast Quality Using Ground Penetrating Radar in Finland
Authors: Silvast M , Nurmikolu A , Wiljanen B , Levomaki M
Published: May 2010

The maintenance of heavy haul railway lines causes considerable cost and in many cases difficulties to rail traffic. Railway infrastructure management in Finland is important because in many locations the same railway lines are used by both freight and passenger trains. Along with the mixed traffic, the cold climate presents challenges in keeping the track in good condition. There is a great demand for economical and non-destructive methods that provide continuous condition information of track structure. In recent years, the ground penetrating radar (GPR) technology for structure inspection has improved to faster systems and better data quality.

This article presents the main results from a research programme that was aimed to identify different GPR-based railway ballast degradation classes and to develop a preventative maintenance planning system. An extensive reference sampling and laboratory analysis has been performed to aid in developing the GPR-based classification method for qualifying the ballast fouling. Classification is made by a fouling index, which is calculated from the frequency contents of the GPR signal. This quality classification can be utilized in the planning of undercutting programmes.
Determination of the risk due to explosions in railway systems
Authors: Larcher M , Casadei F , Giannopoulos G , Solomos G , Planchet J -L , Rochefrette A
Published: May 2010

Land mass transport systems have an open architecture and are vulnerable to terrorist attacks. In case of an explosion inside trains or stations, the risk of injuries and fatalities may be mitigated by properly strengthening and optimizing these structures. This risk depends on the peak overpressure and impulse, which are estimated here using numerical simulations, and is determined by special probit functions using the pressure–time curve calculated at each fluid point. The geometry of the structures investigated is obtained using a three-dimensional laser-scanning technology. Fluid–structure interaction (FSI) calculations have been performed, and for long, tube-like trains channelling effects have been considered. Several materials are used to describe the structural part of the models. A special FSI technique is presented, whereby a structure can be embedded in a fluid mesh without connection to the fluid nodes. This procedure avoids problems after the element erosion due to failure of the structure, e.g. of the glass. The results of case studies are shown in terms of structural displacements and the risk inside a metro line station, a train carriage, and a long train. The effects of venting areas, internal obstacles, such as seats, and passengers themselves to the air blast wave and the associated risk are examined and assessed.
New robust control strategy for module manipulators via sliding mode control with an extended state observer
Authors: Shi X P , Liu S R , Liu F
Published: May 2010

This paper proposes a robust control strategy for module manipulators based on sliding mode control (SMC) and an extended state observer (ESO). First, the nth-order system function is reduced into a first-order function whose argument is the sliding mode. Based on the generalized system, the structured and/or unstructured system non-linear uncertainties are lumped together to form a gross uncertainty which can be estimated by the ESO as an extended state in real time. Then, a controller of the generalized system is designed using SMC based on the extended state. The stability of the system is strictly analysed via the Lyapunov stability theorem approach. This method is applied to the control problem for robot manipulators. Trajectory tracking problems of the joints in a PowerCube robot manipulator are investigated with simulations to validate the analysis.
Fault-tolerant control for a near space vehicle with a stuck actuator fault based on a Takagi-Sugeno fuzzy model
Authors: Gao Z , Jiang B , Shi P , Xu Y
Published: May 2010

Based on both adaptive and fuzzy control techniques, this paper proposes a fault-tolerant control (FTC) approach for near space vehicle (NSV) re-entry attitude dynamics with a stuck actuator fault. A Takagi-Sugeno fuzzy model is used to describe complex NSV attitude dynamics. The principle of this FTC approach is to design an iterative learning observer, which is used to estimate the system state and produce control input adjustment and then to reconfigure the control law to compensate for the effect of the stuck actuator. The FTC scheme ensures that the NSV output dynamics asymptotically track that of a reference model under both fault-free conditions and with a stuck actuator. The boundedness of the error dynamics is analysed using the Lyapunov stability theory. Finally, simulation results are given to illustrate the effectiveness and potential of the proposed FTC technique.
Staffing Call Centers with Uncertain Demand Forecasts: A Chance-Constrained Optimization Approach
Authors: Gurvich Itai , Luedtke James , Tezcan Tolga
Published: May 2010

We consider the problem of staffing call centers with multiple customer classes and agent types operating under quality-of-service (QoS) constraints and demand rate uncertainty. We introduce a formulation of the staffing problem that requires that the QoS constraints are met with high probability with respect to the uncertainty in the demand rate. We contrast this chance-constrained formulation with the average-performance constraints that have been used so far in the literature. We then propose a two-step solution for the staffing problem under chance constraints. In the first step, we introduce a random static planning problem (RSPP) and discuss how it can be solved using two different methods. The RSPP provides us with a first-order (or fluid) approximation for the true optimal staffing levels and a staffing frontier. In the second step, we solve a finite number of staffing problems with known arrival rates—the arrival rates on the optimal staffing frontier. Hence, our formulation and solution approach has the important property that it translates the problem with uncertain demand rates to one with known arrival rates. The output of our procedure is a solution that is feasible with respect to the chance constraint and nearly optimal for large call centers.
A novel mutant-enriched liquidchip technology for the qualitative detection of somatic mutations in KRAS gene from both serum and tissue samples
Authors: Wu Shiyang , Zhu Zeyao , He Jiaying , Luo Xiaodi , Xu Jiasen , Ren-Heidenreich Lifen
Published: May 2010

Background: Somatic mutations in the KRAS gene have been reported to confer drug resistance to epidermal growth factor receptor tyrosine kinase inhibitors and some monoclonal antibodies. However, current DNA mutation detection technologies are primarily DNA sequencing-based and not high throughput, nor sensitive enough to meet clinical needs.

Methods: A mutant-enriched PCR method was designed by introducing a unique restriction enzyme site to the PCR product. This allowed the wild-type KRAS sequence to be selectively removed by restriction enzyme digestion before application to the Luminex liquidchip system.

Results: A total of 100 copies of mutant KRAS DNA fragment mixed with 1×105 copies of the wild-type KRAS DNA could be detected to achieve a sensitivity of 0.1%. This technology is currently used for clinical testing of KRAS somatic mutations for the purpose of pharmacogenomic evaluation. Serum samples from 109 patients with non-small cell lung cancer were tested and 34 mutations were detected (34/109). The formalin-fixed and paraffin-embedded samples from 60 patients with colorectal cancer were tested and 19 mutations were detected (19/60).

Conclusions: A novel, qualitative, sensitive, reliable and high throughput liquidchip technology has been developed for detecting KRAS mutations using clinical serum and formalin-fixed and paraffin-embedded samples.

Clin Chem Lab Med 2010;48:1103–6.
Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis
Authors: Chen Wei-ping , Bao Jia-peng , Feng Jie , Hu Peng-fei , Shi Zhong-li , Wu Li-dong
Published: May 2010

Background: The goal of this study was to investigate the distribution of visfatin in paired serum and synovial fluid (SF) samples from patients with osteoarthritis (OA), and in serum from healthy controls. In addition, we wished to determine the potential sources of visfatin in joint tissue.

Methods: Twenty-three patients with OA requiring total knee arthroplasty (TKA), 17 healthy subjects and ten donors requiring amputation were included in the study. Concentrations of visfatin in serum and SF were analyzed using an enzyme-linked immunosorbent assay (ELISA). The concentration of visfatin was also measured in conditioned media from cultured joint tissues.

Results: We found serum visfatin concentrations to be higher in patients with OA compared to healthy controls (p<0.05), and SF-visfatin concentrations exceeded those in paired serum (p=0.004). In addition, infrapatellar fat pad and synovium were important sources of visfatin, while osteophytes released largest amounts of visfatin. Therefore, osteophytes can be considered a major source of visfatin in the knee joint in patients with OA.

Conclusions: These results suggest that visfatin may be involved in the pathophysiology of OA and may have local effects in the joint during the process of OA.

Clin Chem Lab Med 2010;48:1141–5.
Effects of LY117018 (a SERM analog of raloxifene) on tumor suppressor proteins and proliferation of breast cancer cells
Authors: Dinda Sumi , Sanchez Amelita , Moudgil Virinder K.
Published: May 2010

We have previously shown that presence of estradiol (E2) in the growth medium causes (i) proliferation of T47D breast cancer cells, (ii) elevation of p53 levels, and (iii) hyperphos-phorylation of retinoblastoma protein (pRb). In the present study, we examined the expression of p53, phosphorylation state of pRb and proliferation of T47D cells in the presence of LY117018 (Courtesy of Lilly Research Laboratories), an analog of raloxifene, which is a known selective estrogen receptor modulator (SERM). The cells grown in charcoal-treated serum were treated with 1 nM E2 or different concentrations of LY117018 for 24 h. E2 or LY117018 treatments caused a 2- to 3-fold increase in the level of p53 and hyperphosphorylation of pRb. E2 treatment increased cell proliferation, whereas LY117018 treatment had no such effect but inhibited the E2-dependent cell proliferation. E2 and LY117018 treatments of T47D cells also caused differential effects on intracellular structures. Thus, LY117018 treatment induces changes in the level/activity of p53 and pRb and ultrastructure of T47D cells. Importantly, LY11708 inhibits estrogen-induced cell proliferation while mimicking E2 actions on p53 induction and pRb phosphorylation. The SERM also induced structural alterations in the T47D cells.