bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells
Authors: Usui Tetsuya , Yanagihara Katsunori , Tsukasaki Kunihiro , Murata Ken , Hasegawa Hiroo , Yamada Yasuaki , Kamihira Shimeru
Published: April 2008

Background

HTLV-1 causes adult T-cell leukemia (ATL). Although there have been many studies on the oncogenesis of the viral protein Tax, the precise oncogenic mechanism remains to be elucidated. Recently, a new viral factor, HTLV-1 basic Zip factor (HBZ), encoded from the minus strand mRNA was discovered and the current models of Tax-centered ATL cell pathogenesis are in conflict with this discovery. HBZs consisting of non-spliced and spliced isoforms (HBZ-SI) are thought to be implicated in viral replication and T-cell proliferation but there is little evidence on the HBZ expression profile on a large scale.

Results

To investigate the role of HBZ-SI in HTLV-1 provirus-positive cells, the HBZ-SI and Tax mRNA loads in samples with a mixture of infected and non-infected cells were measured and then adjusted by dividing by the HTLV-I proviral load. We show here that the HBZ-SI mRNA level is 4-fold higher than non-spliced HBZ and is expressed by almost all cells harboring HTLV-1 provirus with variable intensity. The proviral-adjusted HBZ-SI and Tax quantification revealed a characteristic imbalanced expression feature of high HBZ and low Tax expression levels in primary ATL cells or high HBZ and very high Tax levels in HTLV-1-related cell lines (cell lines) compared with a standard expression profile of low HBZ and low Tax in infected cells. Interestingly, according to the mutual Tax and HBZ expression status, HTLV-1-related cell lines were subcategorized into two groups, an ATL cell type with high HBZ and low Tax levels and another type with high Tax and either high or low HBZ, which was closely related to its cell origin.

Conclusion

This is the first comprehensive study to evaluate the mutual expression profile of HBZ and Tax in provirus-positive cells, revealing that there are quantitative and relative characteristic features among infected cells, primary ATL cells, and cell lines.
Investigation of the hydrodynamic properties of a new MRI-resistant programmable hydrocephalus shunt
Authors: Allin David M , Czosnyka Marek , Richards Hugh K , Pickard John D , Czosnyka Zofia H
Published: April 2008

Background

The Polaris valve is a newly released hydrocephalus shunt that is designed to drain cerebrospinal fluid (CSF) from the brain ventricles or lumbar CSF space. The aim of this study was to bench test the properties of the Polaris shunt, independently of the manufacturer.

Methods

The Polaris Valve is a ball-on-spring valve, which can be adjusted magnetically in vivo. A special mechanism is incorporated to prevent accidental re-adjustment by an external magnetic field. The performance and hydrodynamic properties of the valve were evaluated in the UK Shunt Evaluation Laboratory, Cambridge, UK.

Results

The three shunts tested showed good mechanical durability over the 3-month period of testing, and a stable hydrodynamic performance over 45 days. The pressure-flow performance curves, operating, opening and closing pressures were stable. The drainage rate of the shunt increased when a negative outlet pressure (siphoning) was applied. The hydrodynamic parameters fell within the limits specified by the manufacturer and changed according to the five programmed performance levels. Hydrodynamic resistance was dependant on operating pressure, changing from low values of 1.6 mmHg/ml/min at the lowest level to 11.2 mmHg/ml/min at the highest performance level. External programming proved to be easy and reliable. Even very strong magnetic fields (3 Tesla) were not able to change the programming of the valve. However, distortion of magnetic resonance images was present.

Conclusion

The Polaris Valve is a reliable, adjustable valve. Unlike other adjustable valves (except the Miethke ProGAV valve), the Polaris cannot be accidentally re-adjusted by an external magnetic field.
Conventionally-fractionated image-guided intensity modulated radiotherapy (IG-IMRT): a safe and effective treatment for cancer spinal metastasis
Authors: Gong Youling , Wang Jin , Bai Sen , Jiang Xiaoqin , Xu Feng
Published: April 2008

Background

Treatments for cancer spinal metastasis were always palliative. This study was conducted to investigate the safety and effectiveness of IG-IMRT for these patients.

Methods

10 metastatic lesions were treated with conventionally-fractionated IG-IMRT. Daily kilovoltage cone-beam computed tomography (kV-CBCT) scan was applied to ensure accurate positioning. Plans were evaluated by the dose-volume histogram (DVH) analysis.

Results

Before set-up correction, the positioning errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) axes were 0.3 ± 3.2, 0.4 ± 4.5 and -0.2 ± 3.9 mm, respectively. After repositioning, those errors were 0.1 ± 0.7, 0 ± 0.8 and 0 ± 0.7 mm, respectively. The systematic/random uncertainties ranged 1.4–2.3/3.0–4.1 before and 0.1–0.2/0.7–0.8 mm after online set-up correction. In the original IMRT plans, the average dose of the planning target volume (PTV) was 61.9 Gy, with the spinal cord dose less than 49 Gy. Compared to the simulated PTVs based on the pre-correction CBCT, the average volume reduction of PTVs was 42.3% after online correction. Also, organ at risk (OAR) all benefited from CBCT-based set-up correction and had significant dose reduction with IGRT technique. Clinically, most patients had prompt pain relief within one month of treatment. There was no radiation-induced toxicity detected clinically during a median follow-up of 15.6 months.

Conclusion

IG-IMRT provides a new approach to treat cancer spinal metastasis. The precise positioning ensures the implementation of optimal IMRT plan, satisfying both the dose escalation of tumor targets and the radiation tolerance of spinal cord. It might benefit the cancer patient with spinal metastasis.
NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models
Authors: Jensen Michael Rugaard , Schoepfer Joseph , Radimerski Thomas , Massey Andrew , Guy Chantale T , Brueggen Josef , Quadt Cornelia , Buckler Alan , Cozens Robert , Drysdale Martin J , Garcia-Echeverria Carlos , Chène Patrick
Published: April 2008

Introduction

Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the post-translational folding of a large number of client proteins, many of which play essential roles in tumorigenesis. HSP90 has emerged in recent years as a promising new target for anticancer therapies.

Methods

The concentrations of the HSP90 inhibitor NVP-AUY922 required to reduce cell numbers by 50% (GI50 values) were established in a panel of breast cancer cell lines and patient-derived human breast tumors. To investigate the properties of the compound in vivo, the pharmacokinetic profile, antitumor effect, and dose regimen were established in a BT-474 breast cancer xenograft model. The effect on HSP90-p23 complexes, client protein degradation, and heat shock response was investigated in cell culture and breast cancer xenografts by immunohistochemistry, Western blot analysis, and immunoprecipitation.

Results

We show that the novel small molecule HSP90 inhibitor NVP-AUY922 potently inhibits the proliferation of human breast cancer cell lines with GI50 values in the range of 3 to 126 nM. NVP-AUY922 induced proliferative inhibition concurrent with HSP70 upregulation and client protein depletion – hallmarks of HSP90 inhibition. Intravenous acute administration of NVP-AUY922 to athymic mice (30 mg/kg) bearing subcutaneous BT-474 breast tumors resulted in drug levels in excess of 1,000 times the cellular GI50 value for about 2 days. Significant growth inhibition and good tolerability were observed when the compound was administered once per week. Therapeutic effects were concordant with changes in pharmacodynamic markers, including HSP90-p23 dissociation, decreases in ERBB2 and P-AKT, and increased HSP70 protein levels.

Conclusion

NVP-AUY922 is a potent small molecule HSP90 inhibitor showing significant activity against breast cancer cells in cellular and in vivo settings. On the basis of its mechanism of action, preclinical activity profile, tolerability, and pharmaceutical properties, the compound recently has entered clinical phase I breast cancer trials.
Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy
Authors: Niméus-Malmström Emma , Krogh Morten , Malmström Per , Strand Carina , Fredriksson Irma , Karlsson Per , Nordenskjöld Bo , Stål Olle , Östberg Görel , Peterson Carsten , Fernö Mårten
Published: April 2008

Introduction

Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.

Methods

We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.

Results

Within the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).

Conclusion

A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.
Drotrecogin alfa (activated): real-life use and outcomes for the UK
Authors: Rowan Kathryn M , Welch Catherine A , North Emma , Harrison David A
Published: April 2008

Introduction

In March 2001, the results of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study were published, which indicated a 6.1% absolute reduction in 28-day mortality. Drotrecogin alfa (activated; DrotAA) was subsequently approved for use in patients with severe sepsis.

Methods

In December 2002, critical care units in England, Wales and Northern Ireland were invited to participate in an audit of DrotAA. Data for each infusion of DrotAA were linked to case mix and outcome data from a national audit. Use of DrotAA was described and a nonrandomized comparison of effectiveness was conducted.

Results

1,292 infusions of DrotAA were recorded in 112 units; 61% commenced during the first 24 hours in the unit. The majority (77%) of patients had three or more organs failing; lung (42%) and abdomen (40%) were the most common primary sites of infection. Crude hospital mortality was high (45%); at 28 days, only 18% had left acute hospital and 19% were still in the unit. For 30%, the full 96-hour infusion was not completed; 24% of infusions were interrupted; 8.1% experienced one or more serious adverse events, of which 77% were serious bleeding events. Of eight relative risks estimated from individually-matched (0.75 to 0.85) and propensity-matched (0.82 to 0.90) controls, seven were consistent with the results of PROWESS. Restricting the analysis to patients receiving DrotAA during the first 24 hours resulted in larger treatment effects (relative risks 0.62 to 0.81). For all matches, similar patterns were seen across subgroups. No effect of DrotAA was seen for two organs failing or lower severity scores, compared with a significant mortality reduction for three or more organs failing or higher severity scores.

Conclusion

Use of DrotAA was approximately one in 16 for admissions meeting the definition for severe sepsis and with two or more organs failing. Patients receiving DrotAA were younger and more severely ill but were less likely to have serious conditions in their past medical history. Nonrandomized estimates for the effectiveness of DrotAA were consistent with the findings of PROWESS. DrotAA appeared not to be effective in patients with less severe disease.
Genomic context analysis in Archaea suggests previously unrecognized links between DNA replication and translation
Authors: Berthon Jonathan , Cortez Diego , Forterre Patrick
Published: April 2008

Background

Comparative analysis of genomes is valuable to explore evolution of genomes, deduce gene functions, or predict functional linking between proteins. Here, we have systematically analyzed the genomic environment of all known DNA replication genes in 27 archaeal genomes to infer new connections for DNA replication proteins from conserved genomic associations.

Results

Two distinct sets of DNA replication genes frequently co-localize in archaeal genomes: the first includes the genes for PCNA, the small subunit of the DNA primase (PriS), and Gins15; the second comprises the genes for MCM and Gins23. Other genomic associations of genes encoding proteins involved in informational processes that may be functionally relevant at the cellular level have also been noted; in particular, the association between the genes for PCNA, transcription factor S, and NudF. Surprisingly, a conserved cluster of genes coding for proteins involved in translation or ribosome biogenesis (S27E, L44E, aIF-2 alpha, Nop10) is almost systematically contiguous to the group of genes coding for PCNA, PriS, and Gins15. The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis. Interestingly, the gene encoding the S27E protein, also known as metallopanstimulin 1 (MPS-1) in human, is overexpressed in multiple cancer cell lines.

Conclusion

Our genome context analysis suggests specific functional interactions for proteins involved in DNA replication between each other or with proteins involved in DNA repair or transcription. Furthermore, it suggests a previously unrecognized regulatory network coupling DNA replication and translation in Archaea that may also exist in Eukarya.
Type 1-polarized dendritic cells loaded with autologous tumor are a potent immunogen against chronic lymphocytic leukemia
Authors: Lee Je-Jung , Foon Kenneth A , Mailliard Robbie B , Muthuswamy Ravikumar , Kalinski Pawel
Published: April 2008

Induction of active tumor-specific immunity in patients with chronic lymphocytic leukemia (CLL) and other hematologic malignancies is compromised by the deficit of endogenous dendritic cells (DCs). In attempt to develop improved vaccination strategies for patients with CLL and other tumors with poorly identified rejection antigens, we tested the ability of ex vivo-generated DCs to cross-present the antigens expressed by CLL cells and to induce CLL-specific, functional CTL responses. Monocyte-derived DCs from CLL patients were induced to mature using a “standard” cytokine cocktail (in IL-1β, TNF-α, IL-6, and PGE2) or using an α-type 1-polarized DC (αDC1) cocktail (in IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and were loaded with γ-irradiated, autologous CLL cells. αDC1 from CLL patients expressed substantially higher levels of multiple costimulatory molecules (CD83, CD86, CD80, CD11c, and CD40) than standard DCs (sDCs) and immature DCs, and their expression of CCR7 showed intermediate level. αDC1 secreted substantially higher (10–60 times) levels of IL-12p70 than sDCs. Although αDC1 and sDCs showed similar uptake of CLL cells, αDC1 induced much higher numbers (range, 2.4–38 times) of functional CD8+ T cells against CLL cells. The current demonstration that autologous tumor-loaded αDC1 are potent inducers of CLL-specific T cells helps to develop improved immunotherapies of CLL.
Mammography Before Diagnosis Among Women Age 80 Years and Older With Breast Cancer
Authors: Badgwell Brian D. , Giordano Sharon H. , Duan Zhigang Z. , Fang Shenying , Bedrosian Isabelle , Kuerer Henry M. , Singletary S. Eva , Hunt Kelly K. , Hortobagyi Gabriel N. , Babiera Gildy
Published: April 2008

Purpose

Screening mammography guidelines for patients age 80 years and older are variable. We determined the effect of mammography use on stage at breast cancer diagnosis and survival among women of this age range.

Patients and Methods

We used the linked Surveillance, Epidemiology, and End Results–Medicare database to evaluate 12,358 women ≥ 80 years of age diagnosed with breast cancer between 1996 and 2002. Patients were grouped according to number of mammograms during the 60 months before diagnosis: nonusers (0 mammograms), irregular users (one to two mammograms), and regular users (three or more mammograms). Effects of mammography on disease stage (I to IIa v IIb to IV) and survival were determined by logistic regression and Cox proportional hazards analyses.

Results

Percentages of women with nonuse, irregular use, and regular use of mammography during the 5 years preceding diagnosis were 49%, 29%, and 22%, respectively. On multivariate analysis, patients were 0.37 times less likely to present with late-stage cancer for each mammogram obtained (odds ratio, 0.63; 95% CI, 0.63 to 0.67). Breast cancer–specific 5-year survival among nonusers was 82%, that among irregular users was 88%, and that among regular users was 94%. However, survival from causes other than breast cancer was also associated with mammography use, suggesting a bias for healthier patients to undergo mammography.

Conclusion

Regular mammography among women ≥ 80 years of age was associated with earlier disease stage, although improved survival remains difficult to demonstrate. Health care providers should consider discussing the potential benefits of screening mammography with their older patients, particularly for those without significant comorbidity.
Granulocyte-Macrophage Colony-Stimulating Factor Potentiates Rituximab in Patients With Relapsed Follicular Lymphoma: Results of a Phase II Study
Authors: Cartron Guillaume , Zhao-Yang Lu , Baudard Marion , Kanouni Tarik , Rouillé Valérie , Quittet Philippe , Klein Bernard , Rossi Jean-Francois
Published: April 2008

Purpose

We hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF) could potentiate the clinical activity of rituximab given its individual and cooperative effects on FcγRIIa- and FcγRIIIa-expressing cells. A phase II clinical study combining GM-CSF and rituximab was initiated in patients with relapsed follicular lymphoma (FL) to determine the clinical and biologic responses, as well as safety of the combination.

Patients and Methods

Thirty three patients with relapsed FL were treated with GM-CSF 5 μg/kg/d on days 1 to 8 and rituximab 375 mg/m2on day 5 of each 21-day cycle for four cycles. Clinical response and tolerability were examined according to international criteria. Biologic monitoring included evaluation of immune cells involved in rituximab activity.

Results

Of 33 evaluated patients, a 70% overall response rate (complete response plus complete response unconfirmed, 45%) and a median progression-free survival (PFS) of 16.5 months were achieved. Outcome was influenced by the quality of response and the Follicular Lymphoma International Prognostic Index (FLIPI), where low- and intermediate-risk FLIPI groups were associated with significantly better PFS. After treatment there was a significant increase in granulocyte and monocyte counts. Examination of dendritic cell response showed an overall increase in plasmacytoid dendritic cells, especially in non-complete response patients, after treatment. Addition of GM-CSF did not impair tolerance to rituximab, and adverse events were rare and mild.

Discussion

GM-CSF plus rituximab results in high response rates, along with a tolerable safety profile in patients with relapsed or progressive FL. The improved efficacy over rituximab monotherapy may be due to increases seen in monocyte, granulocyte, and dendritic cell populations.
HIV-Specific Differences in Outcome of Squamous Cell Carcinoma of the Anal Canal: A Multicentric Cohort Study of HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy
Authors: Oehler-Jänne Christoph , Huguet Florence , Provencher Sawyna , Seifert Burkhardt , Negretti Laura , Riener Marc-Oliver , Bonet Marta , Allal Abdelkarim S. , Ciernik I. Frank
Published: April 2008

Purpose

To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART).

Patients and Methods

A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated.

Results

HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04).

Conclusion

Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.
Individualizing Treatment of Patients With Myeloma in the Era of Novel Agents
Authors: San-Miguel Jesús , Harousseau Jean-Luc , Joshua Douglas , Anderson Kenneth C.
Published: April 2008

Progress in the understanding of multiple myeloma (MM) cell biology has led to the identification of new relevant prognostic factors and subsequently different risk groups. This concept, together with the recent discovery of new drugs with novel mechanisms of action, will probably lead to individualized treatment according to the different patients’ characteristics. In this review, we focus on current available agents already approved for MM, and discuss individualized treatment approaches for both transplantation candidates (subdivided into standard and high-risk patients) and elderly patients. Future progress in MM will be based on using science to inform the design of the optimal combined treatments, and high throughput assays that can assess the ability of combination therapies to induce death of MM cells, both alone and in the bone marrow microenvironment.
Two approaches to coil impedance calculation of eddy current sensor
Authors: Yating Yu , Pingan Du
Published: April 2008

Eddy current (EC) sensor detects measurand by the change of coil impedance, which is introduced by coupling the magnetic energy between coil and measurement target. Therefore, it is of great significance for both the forward and inverse eddy current problems to study on the approaches to coil impedance calculation. In the current paper, two approaches are presented to calculate coil impedance of EC sensor. First, the theoretical calculation model of coil impedance is simplified as an air-cored cylindrical coil, over an infinite measurement target. And the integral expression of coil impedance is derived according to the sensor operation principle and electromagnetic field theory. Then, the integral expression is expanded as series form in cylindrical coordinate system in order to compute the coil impedance easily, and computed using MathematicaTM. Next, based on the finite element modeling theory, two different finite element models of eddy current measurement system are built. The infinite boundary in mode1 is truncated, while in model 2, it is simulated completely by an infinite element. Furthermore, the appropriate location where the air domain is truncated at is determined. Finally, the coil impedance and the magnetic distribution of eddy current testing system are obtained by finite element method, respectively. By comparison, the results from the theoretical calculation approach and finite element method are in very good agreement, and the accuracy of two approaches is validated with each other.
A numerical study of the nozzle/diffuser micropump
Authors: Yang K-S , Chen I-Y , Chien K-H , Wang C-C
Published: April 2008

This study numerically investigates the performance of micronozzle/diffuser pump subject to the influence of frequency, opening angle, geometric dimension, and amplitude. For the effect of geometric dimension, the effect of chamber length is far more important than that of chamber depth because it can provide much more effective pumping volume. It is found that the net flowrate of a micropump increased with pumping frequency and opening angle. However, a level-off phenomenon of the net flowrate versus amplitude is seen at amplitudes nearby 150–200 μm and at an opening angle above 10°. This phenomenon is associated with two factors that compensate with each other. One is the free jet flow from the outlet that overturns and blocks the flow from the inlet. The other is the reduction of the strength of jet flow at a larger amplitude owing to effective increase of cross-sectional area.
Hydraulic actuation of multi-body structures through large-scale motions. Part 2: Controller design and performance
Authors: Branson D T , Keogh P S , Tilley D G
Published: April 2008

This paper addresses a controller design methodology for the hydraulic actuation of non-linear multi-body systems. It takes account of system uncertainties, envisaged system changes through added mass, positioning speed requirements, and vibration control. A mathematical model developed in the companion paper, Part 1, describes an experimental multi-body structure that is actuated by a hydraulic system. It is used to generate H∞-based position and active vibration controllers to meet the actuation requirements at the design stage. Experimental tests were undertaken with the developed H∞ controllers to demonstrate their accuracy and stability of motion control. The results are compared to ‘base level’ tests completed using a more traditional proportional-integral (PI) controller. In contrast with the instability experienced using PI control, the design process associated with the H∞ controllers ensures accurate closed loop stability over the range of system variations.
Power and efficiency optimization for combined Brayton and two parallel inverse Brayton cycles. Part 1: Description and modelling
Authors: Chen L , Zhang W , Sun F
Published: April 2008

A thermodynamic model for open combined Brayton and two parallel inverse Brayton cycles is established using finite-time thermodynamics in part A of the current paper. The flow processes of the working fluid with the pressure drops of the working fluid and the size constraints of the real power plant are modelled. There are 17 flow resistances encountered by the gas stream for the combined Brayton and two parallel inverse Brayton cycles. Six of these, the friction through the blades and vanes of the compressors and the turbines, are related to the isentropic efficiencies. The remaining flow resistances are always present because of the changes in flow cross-section at the compressor inlet of the top cycle, combustion inlet and outlet, turbine outlet of the top cycle, turbine outlets of the bottom cycle, heat exchanger inlets, and compressor inlets of the bottom cycle. These resistances control the air flowrate and the net power output. The relative pressure drops associated with the flow through various cross-sectional areas are derived as functions of the compressor inlet relative pressure drop of the top cycle. The analytical formulae about the relations between power output, thermal conversion efficiency, and the compressor pressure ratio of the top cycle are derived with the 17 pressure drop losses in the intake, compression, combustion, expansion, and flow process in the piping, the heat transfer loss to ambient, the irreversible compression and expansion losses in the compressors and the turbines, and the irreversible combustion loss in the combustion chamber. The performance of the model cycle is optimized by adjusting the compressor inlet pressure of the bottom cycles, the mass flowrate and the distribution of pressure losses along the flow path in part B of the current paper.
Motion adaptation of cam-follower systems by varying input speeds
Authors: Yan H-S , Tsai W-J
Published: April 2008

Cam mechanisms are widely applied in automatic production machines. Variable cam speeds provide a flexible tool for adapting the follower motion to the working condition changes. The current study proposes the methods for generating the needed follower motion and adjusting to the required times of periods in the cam motion program. The Bezier function is used to express the cam speed trajectory, whose motion characteristics and boundary continuities are to be decided by the control points. An optimization design model for generating the required motion is then built to specify the control points of this trajectory. Also, the relations are developed that cope with connection continuities and period time managements among the motion periods of a complete cam rotation. Two design examples in component transferring and metal-sheet forming applications are given for illustrating the proposed design approaches.
Evaluation of the reduction of dynamical coupling for robot manipulators
Authors: Herman P
Published: April 2008

The problem of evaluation of the reduction of dynamical coupling in rigid serial manipulators is presented in the current paper. The proposed strategy is based on first-order equations of motion expressed in terms of normalized generalized velocity components, which result from decomposition of the manipulator mass matrix. The principal activity of the study relies on an algorithm in which some evaluation criteria as well as some indexes are used. The presented approach is important, mainly for manipulators with a direct drive arm at their design stage. Simulation results on a three-degree-of-freedom (3-DOF) spatial manipulator are given in order to illustrate the offered method.
Forced vibration analysis for dynamic coupling of finite-element spring-reduced suspension system
Authors: Kang Jaeyoung
Published: April 2008

The current paper studies the dynamic behaviour of a coil spring in a vehicle suspension system. A portion of the coil spring is contacted with the top and bottom spring pads. The contact interface is modelled as a set of linear spring elements on the contact nodes of the coil spring. The eigensensitivity analysis is conducted to investigate the frequency variation of the stiffness-coupled system with respect to the contact stiffness variation. In the forced vibration analysis, the transfer function through the coil spring is obtained. The contribution of the coil spring modes to the load transfer is calculated by the modal contribution factor. It is shown that some of the longitudinal and bending vibration modes participate on the load transfer.
A simplified tumour model established via Epstein-Barr virus-encoded, nasopharyngeal carcinoma-derived oncogene latent membrane protein 1 in immunocompetent mice
Authors: Chow Kai-Ping N , Wu C C , Chang H Y , Chang C , Chang Y S
Published: April 2008

Summary

The expression and immune modulation of Epstein-Barr virus-encoded oncogene latent membrane protein 1 (N-LMP1) is essential in the pathogenesis of nasopharyngeal carcinoma. In previous studies, cell transformation has been induced by the expression of EBV-encoded N-LMP1 in non-tumour BALB/c-3T3 cells and these cells have then been used to form tumours in T-cell-deficient nude mice. However, studies using this model have been limited by the lack of a competent immune system. To facilitate the study of immune components in N-LMP1-driven oncogenesis, we herein developed a simplified N-LMP1-derived tumour model in immunocompetent mice. Cell transformation was induced by the expression of N-LMP1 in BALB/c-3T3 cells, and these transformants were used to induce oncogenesis in BALB/c mice. In contrast to the 100% successful tumour-induction rate in nude mice treated with monodispersed transformed cells, the tumour incidence in BALB/c mice was only 5–36%. However, the transplantation of tumour fragments into BALB/c mice yielded a reproducible tumour-induction rate of >85%, which is acceptable for most of the research needs. This novel model of N-LMP1-directed oncogenesis in an immunocompetent environment may serve as an important platform for the future assessment of N-LMP1-targeted tumour therapies.
Upgrading mouse health and welfare: direct benefits of a large-scale rederivation programme
Authors: Fray M D , Pickard A R , Harrison M , Cheeseman M T
Published: April 2008

Summary

We report the outcome of a 30-month programme to rederive 310 specific pathogen-free mouse strains to populate a new individually ventilated cage barrier facility at the Mary Lyon Centre (MLC), Medical Research Council (MRC) Harwell. The mice were rederived in a self-contained quarantine suite and embryo-recipient females were health-screened to assess microbiological status, before moving their offspring into the new facility. The MLC currently houses approximately 49,000 mice in about 9750 cages and we have 30 months of follow-up health screen data. Embryo rederivation and hysterectomy have high safety margins; however, the precaution of performing the programme in isolators facilitated the containment and decontamination of two mouse hepatitis virus (MHV) infection outbreaks. Rederivation of the colony has eliminated endemic MHV, mouse adenovirus type 2 (MAV-2), Theiler's murine encephalomyelitis virus, pinworms, intestinal protozoa, Pasteurella pneumotropica, Helicobacter spp. and mites. The improvements in microbiological status have had notable benefits for mouse health and welfare and the science at MRC Harwell. Previously important clinical entities such as sudden death associated with lactation ileus in C3H/HeH mice, early weight loss associated with inflammatory bowel disease in B6-TgN(HDexon1)61Gpb and B6-TgN(HD82Gln)81Dbo (Huntington) mice and early weight loss in male mice mutagenized with N-ethyl- N-nitrosourea have been markedly reduced or eliminated.
The effects on heart rate and temperature of mice and vas deferens responses to noradrenaline when their cage mates are subjected to daily restraint stress
Authors: Gilmore A J , Billing R L , Einstein R
Published: April 2008

Summary

Performing stressful procedures in view of cage mates may cause stress in observer animals. However, it is not known if stressful procedures performed in close proximity to, but not in view of cage mates are stressful for the (observer) cage mates. Radiotelemetry and postmortem in vitro studies of the vas deferens were used to determine the effects of stress on observers. Heart rate (HR) and core body temperature (cBT) were recorded for 1 h following weighing of a cage mate or 1 h during restraint of a cage mate and the hour following return of the restrained mouse to the cage. This procedure was repeated daily for 15 days. HR and cBT were increased in observers during both restraint and weighing of cage mates. Analysis of the area under the curve showed that HR and cBT in observers were significantly higher during restraint of a cage mate than after weighing of a cage mate. When mice were returned to the cage after weighing or restraint, HR and cBT were significantly higher in the cage mates of restrained animals. Comparison between days 1, 3, 7 and 14 found that, as the experiment progressed, HR and cBT were significantly reduced in the observer mice during the hour following return of the cage mates after restraint. Results from previous studies have shown that chronic stress causes the vas deferens to become hypersensitive to exogenous application of noradrenaline (NAd). In this study, vas deferens from observers of restraint had a significantly increased response to NAd. These results indicate that stressful procedures should be conducted in isolation from other mice.
DcpS scavenger decapping enzyme can modulate pre-mRNA splicing
Authors: Shen Vincent , Liu Hudan , Liu Shin-Wu , Jiao Xinfu , Kiledjian Megerditch
Published: April 2008

The human scavenger decapping enzyme, DcpS, functions to hydrolyze the resulting cap structure following cytoplasmic mRNA decay yet is, surprisingly, a nuclear protein by immunofluorescence. Here, we show that DcpS is a nucleocytoplasmic shuttling protein that contains separable nuclear import and Crm-1-dependent export signals. We postulated that the presence of DcpS in both cellular compartments and its ability to hydrolyze cap structure may impact other cellular events dependent on cap-binding proteins. An shRNA-engineered cell line with markedly diminished DcpS levels led to a corresponding reduction in cap-proximal intron splicing of a reporter minigene and endogenous genes. The impaired cap catabolism and resultant imbalanced cap concentrations were postulated to sequester the cap-binding complex (CBC) from its normal splicing function. In support of this explanation, DcpS efficiently displaced the nuclear cap-binding protein Cbp20 from cap structure, and complementation with Cbp20 reversed the reduced splicing, indicating that modulation of splicing by DcpS is mediated through Cbp20. Our studies demonstrate that the significance of DcpS extends beyond its well-characterized role in mRNA decay and involves a broader range of functions in RNA processing including nuclear pre-mRNA splicing.
Selection and characterization of anti-NF-κB p65 RNA aptamers
Authors: Wurster Susan E. , Maher L. James
Published: April 2008

NF-κB transcription factors include a group of five mammalian proteins that form hetero- or homodimers and regulate hundreds of target genes involved in acute inflammation, HIV-1 transcription activation, and resistance to cancer therapy. We previously used in vitro selection to develop a small RNA aptamer (anti-p50) that binds the DNA-binding domain of NF-κB p502with low nanomolar affinity but does not bind NF-κB p652. Here, we report the in vitro selection of anti-NF-κB p65 RNA aptamers using parallel in vitro selections with either a fully randomized RNA library or a degenerate RNA library based on the primary sequence of the 31-nucleotide anti-p50 RNA aptamer. We report the characterization of these aptamers with respect to NF-κB target specificity, affinity, minimal sequence requirements, secondary structure, and competition with DNA κB sites. These results expand opportunities for artificial inhibition of NF-κB transcription factor dimers containing p65 subunits.
A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L
Authors: Townsend Hannah L. , Jha Babal K. , Han Jian-Qiu , Maluf N. Karl , Silverman Robert H. , Barton David J.
Published: April 2008

Ribonuclease L (RNase L) is a latent endoribonuclease in an evolutionarily ancient interferon-regulated dsRNA-activated antiviral pathway. 2′–5′ oligoadenylate (2–5A), the product of dsRNA-activated oligoadenylate synthetases (OASes), binds to ankyrin repeats near the amino terminus of RNase L, initiating a series of conformational changes that result in the activation of the endoribonuclease. A phylogenetically conserved RNA structure within group C enteroviruses inhibits the endoribonuclease activity of RNase L. In this study we report the mechanism by which group C enterovirus RNA inhibits RNase L. Viral RNA did not affect 2–5A binding to RNase L. Rather, the viral RNA inhibited the endoribonuclease domain. We used purified RNase L, purified 2–5A, and an RNA substrate with a 5′ fluorophore and 3′ quencher in FRET assays to measure inhibition of RNase L activity by the viral RNA. The group C enterovirus RNA was a competitive inhibitor of the endoribonuclease with a Ki of 34 nM. Consistent with the kinetic profile of a competitive inhibitor, the viral RNA inhibited the constitutively active endoribonuclease domain of RNase L. We call this viral RNA the RNase L competitive inhibitor RNA (RNase L ciRNA).
Tabu Search-Enhanced Graphical Models for Classification in High Dimensions
Authors: Bai Xue , Padman Rema , Ramsey Joseph , Spirtes Peter
Published: April 2008

Data sets with many discrete variables and relatively few cases arise in health care, e-commerce, information security, text mining, and many other domains. Learning effective and efficient prediction models from such data sets is a challenging task. In this paper, we propose a tabu search-enhanced Markov blanket (TS/MB) algorithm to learn a graphical Markov blanket model for classification of high-dimensional data sets. The TS/MB algorithm makes use of Markov blanket neighborhoods: restricted neighborhoods in a general Bayesian network based on the Markov condition. Computational results from real-world data sets drawn from several domains indicate that the TS/MB algorithm, when used as a feature selection method, is able to find a parsimonious model with substantially fewer predictor variables than is present in the full data set. The algorithm also provides good prediction performance when used as a graphical classifier compared with several machine-learning methods.
A Review and Evaluation of Multiobjective Algorithms for the Flowshop Scheduling Problem
Authors: Minella Gerardo , Ruiz Rubén , Ciavotta Michele
Published: April 2008

This paper contains a complete and updated review of the literature for multiobjective flowshop problems, which are among the most studied environments in the scheduling research area. No previous comprehensive reviews exist in the literature. Papers about lexicographical, goal programming, objective weighting, and Pareto approaches have been reviewed. Exact, heuristic, and metaheuristic methods have been surveyed. Furthermore, a complete computational evaluation is also carried out. A total of 23 different algorithms including both flowshop-specific methods as well as general multiobjective optimization approaches have been tested under three different two-criteria combinations with a comprehensive benchmark. All methods have been studied under recent state-of-the-art quality measures. Parametric and nonparametric statistical testing is profusely employed to support the observed performance of the compared methods. As a result, we have identified the best-performing methods from the literature, which along with the review, constitutes a reference work for further research.
E Pluribus Unum: Framing, Matching, and Form Emergence in U.S. Television Broadcasting, 1940–1960
Authors: Perretti Fabrizio , Negro Giacomo , Lomi Alessandro
Published: April 2008

Recent research holds that new organizational forms emerge from the identity of candidate organizations that enter a domain. In this study we argue that emergence of a new form, which is ultimately based on validation by external audiences, depends on two mechanisms: identity framing, i.e., how audiences perceive and frame the identity of an emerging organizational domain, and identity matching, i.e., the match between the identity of the domain and the identity of candidates. Accordingly, form emergence is best characterized as contextual rather than as an inherent attribute of the categories of candidate organizations. Using data on the U.S. commercial television industry from 1940 to 1960, we explore how entry rates of TV stations were affected by audiences' expectations about the identity of the nascent domain and by the densities of organizations with different origins. We find evidence that focused expectations expressed through public discourse about media, and the number of stations coming from radio broadcasting increased entry rates. We reconcile our findings with existing theory on the emergence of organizational forms by pointing to the joint relevance of domain-related and candidate-related identities.
Supervisor trainees' and their supervisors' perceptions of attainment of knowledge and skills: An empirical evaluation of a psychotherapy supervisor training programme
Authors: Sundin Eva C. , Ögren Marie‐Louise , Boëthius Siv Boalt
Published: April 2008

Objectives

This study aimed to evaluate the success of a 2‐year, part‐time training programme for psychotherapy supervisors. A second aim was to examine factors that might contribute to perceived knowledge and skills attainment during the training course.

Design

This is a naturalistic, longitudinal study where several measures are used to examine group process and outcome.

Methods

Supervisor trainees' (N = 21) and their facilitators' (N = 6) ratings of learning (knowledge and skills), relations to the supervisor and supervision group, usage of the group, and supervisor style were completed at three time points.

Results

The findings suggested that both trainees and their supervisors perceived that the trainees attained a substantial amount of knowledge and skills during the course. In accordance with the literature and expectations, the regression analysis suggested a strong negative association between a strong focus on group processes in the initial and middle phases of the training and perceived knowledge and skills attainment in the final phase of the training. The expected, positive role of relations among trainees in the supervision group in the first half of the training and perceived knowledge and skills attainment in the final part of the training was obtained, whilst the hypothesized significance of the relationship between trainee and supervisor did not receive support.

Conclusions

The supervisory course seemed to provide a training that allowed trainees to attain knowledge and skills that are necessary for psychotherapy supervisors. The results of this pilot study also emphasize the need of more research on learning in the context of group supervision in psychotherapy.