bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface
Authors: Achour Lamia , Scott Mark G. H. , Shirvani Hamasseh , Thuret Alain , Bismuth Georges , Labbé-Jullié Catherine , Marullo Stefano
Published: December 2008

The association of CD4, a glycoprotein involved in T-cell development and antigen recognition, and CC chemokine receptor 5 (CCR5), a chemotactic G protein–coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for HIV. We observed that the majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relatively low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration-dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell-surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cellular distribution of CXCR4, the other HIV coreceptor. These results reveal a previously unappreciated role of CD4, which contributes to regulating CCR5 export to the plasma membrane.
Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB
Authors: Zhao Tiejun , Yasunaga Jun-ichirou , Satou Yorifumi , Nakao Mitsuyoshi , Takahashi Masahiko , Fujii Masahiro , Matsuoka Masao
Published: December 2008

Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). The activation of NF-κB by Tax has been reported to play a crucial role in HTLV-1–induced transformation. The HTLV-1 bZIP factor (HBZ), which is encoded by an mRNA of the opposite polarity of the viral genomic RNA, is involved in both T cell proliferation and suppression of Tax-mediated viral gene transcription, suggesting that HBZ cooperates closely with Tax. In the present study, we observed that HBZ specifically suppressed NF-κB–driven transcription mediated by p65 (the classical pathway) without inhibiting the alternative NF-κB signaling pathway. In an immunoprecipitation assay, HBZ bound to p65 and diminished the DNA binding capacity of p65. In addition, HBZ induced p65 degradation through increasing the expression of the PDLIM2 gene, which encodes a ubiquitin E3 ligase for p65. Finally, HBZ actually repressed the transcription of some classical NF-κB target genes, such as IL-8, IL2RA, IRF4, VCAM-1, and VEGF. Selective suppression of the classical NF-κB pathway by HBZ renders the alternative NF-κB pathway predominant after activation of NF-κB by Tax or other stimuli, which might be critical for oncogenesis.
ESKIMO1 is a key gene involved in water economy as well as cold acclimation and salt tolerance
Authors: Bouchabke-Coussa Oumaya , Quashie Marie-Luce , Seoane-Redondo Jose , Fortabat Marie-Noelle , Gery Carine , Yu Agnes , Linderme Daphné , Trouverie Jacques , Granier Fabienne , Téoulé Evelyne , Durand-Tardif Mylène
Published: December 2008

Background

Drought is a major social and economic problem resulting in huge yield reduction in the field. Today's challenge is to develop plants with reduced water requirements and stable yields in fluctuating environmental conditions. Arabidopsis thaliana is an excellent model for identifying potential targets for plant breeding. Drought tolerance in the field was successfully conferred to crops by transferring genes from this model species. While involved in a plant genomics programme, which aims to identify new genes responsible for plant response to abiotic stress, we identified ESKIMO1 as a key gene involved in plant water economy as well as cold acclimation and salt tolerance.

Results

All esk1 mutants were more tolerant to freezing, after acclimation, than their wild type counterpart. esk1 mutants also showed increased tolerance to mild water deficit for all traits measured. The mutant's improved tolerance to reduced water supply may be explained by its lower transpiration rate and better water use efficiency (WUE), which was assessed by carbon isotope discrimination and gas exchange measurements. esk1 alleles were also shown to be more tolerant to salt stress.

Transcriptomic analysis of one mutant line and its wild-type background was carried out. Under control watering conditions a number of genes were differentially expressed between the mutant and the wild type whereas under mild drought stress this list of genes was reduced. Among the genes that were differentially expressed between the wild type and mutant, two functional categories related to the response to stress or biotic and abiotic stimulus were over-represented. Under salt stress conditions, all gene functional categories were represented equally in both the mutant and wild type. Based on this transcriptome analysis we hypothesise that in control conditions the esk1 mutant behaves as if it was exposed to drought stress.

Conclusion

Overall our findings suggest that the ESKIMO1 gene plays a major role in plant response to water shortage and in whole plant water economy. Further experiments are being undertaken to elucidate the function of the ESKIMO1 protein and the way it modulates plant water uptake.
The INIS Study. International Neonatal Immunotherapy Study: non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: an international, placebo controlled, multicentre randomised trial
Authors:   The INIS Study Collaborative Group
Published: December 2008

Background

Sepsis is an important cause of neonatal death and perinatal brain damage, particularly in preterm infants. While effective antibiotic treatment is essential treatment for sepsis, resistance to antibiotics is increasing. Adjuvant therapies, such as intravenous immunoglobulin, therefore offer an important additional strategy. Three Cochrane systematic reviews of randomised controlled trials in nearly 6,000 patients suggest that non-specific, polyclonal intravenous immunoglobulin is safe and reduces sepsis by about 15% when used as prophylaxis but does not reduce mortality in this situation. When intravenous immunoglobulin is used in the acute treatment of neonatal sepsis, however, there is a suggestion that it may reduce mortality by 45%. However, the existing trials of treatment were small and lacked long-term follow-up data.

This study will assess reliably whether treatment of neonatal sepsis with intravenous immunoglobulin reduces mortality and adverse neuro-developmental outcome.

Methods and design

A randomised, placebo controlled, double blind trial. Babies with suspected or proven neonatal sepsis will be randomised to receive intravenous immunoglobulin therapy or placebo.

Eligibility criteria

Babies must be receiving antibiotics and have proven or suspected serious infection AND have at least one of the following: birthweight less than 1500 g OR evidence of infection in blood culture, cerebrospinal fluid or usually sterile body fluid OR be receiving respiratory support via an endotracheal tube AND there is substantial uncertainty that intravenous immunoglobulin is indicated.

Exclusion criteria

Babies are excluded if intravenous immunoglobulin has already been given OR intravenous immunoglobulin is thought to be needed OR contra-indicated.

Trial treatment

Babies will be given either 10 ml/kg of intravenous immunoglobulin or identical placebo solution over 4–6 hours, repeated 48 hours later.

Primary outcome

Mortality or major disability at two years, corrected for gestational age.

Data collection

Data will be collected at discharge from hospital and at 2 years of age (corrected for gestation) using a parental questionnaire and a health status questionnaire completed during a face-to-face follow-up appointment with the child's paediatrician.

Trial registration

Current Controlled Trials ISCRTN94984750.
Behavior of osteoblastic cells cultured on titanium and structured zirconia surfaces
Authors: Depprich Rita , Ommerborn Michelle , Zipprich Holger , Naujoks Christian , Handschel Jörg , Wiesmann Hans-Peter , Kübler Norbert R , Meyer Ulrich
Published: December 2008

Background

Osseointegration is crucial for the long-term success of dental implants and depends on the tissue reaction at the tissue-implant interface. Mechanical properties and biocompatibility make zirconia a suitable material for dental implants, although surface processings are still problematic. The aim of the present study was to compare osteoblast behavior on structured zirconia and titanium surfaces under standardized conditions.

Methods

The surface characteristics were determined by scanning electron microscopy (SEM). In primary bovine osteoblasts attachment kinetics, proliferation rate and synthesis of bone-associated proteins were tested on different surfaces.

Results

The results demonstrated that the proliferation rate of cells was significantly higher on zirconia surfaces than on titanium surfaces (p < 0.05; Student's t-test). In contrast, attachment and adhesion strength of the primary cells was significant higher on titanium surfaces (p < 0.05; U test). No significant differences were found in the synthesis of bone-specific proteins. Ultrastructural analysis revealed phenotypic features of osteoblast-like cells on both zirconia and titanium surfaces.

Conclusion

The study demonstrates distinct effects of the surface composition on osteoblasts in culture. Zirconia improves cell proliferation significantly during the first days of culture, but it does not improve attachment and adhesion strength. Both materials do not differ with respect to protein synthesis or ultrastructural appearance of osteoblasts. Zirconium oxide may therefore be a suitable material for dental implants.
Lemierre's syndrome due to community-acquired meticillin-resistant Staphylococcus aureus infection and presenting with orbital cellulitis: a case report
Authors: Kadhiravan Tamilarasu , Piramanayagam Paramasivan , Banga Amit , Gupta Rajiva , Sharma Surendra K
Published: December 2008

Introduction

Lemierre's syndrome is septic thrombophlebitis of the internal jugular vein leading to metastatic septic complications following an oropharyngeal infection. It is usually caused by the anaerobe, Fusobacterium necrophorum. Of late, meticillin-resistant Staphylococcus aureus is increasingly being recognised as a cause of community-acquired skin and soft tissue infections. We report a rare case of Lemierre's syndrome caused by community-acquired meticillin-resistant Staphylococcus aureus infection.

Case presentation

A previously healthy 16-year-old girl presented with fever of 13 days duration, painful swelling around the right eye and diplopia followed by the appearance of pulmonary infiltrates. Imaging studies confirmed the clinical suspicion of bilateral jugular venous thrombosis with septic pulmonary embolism. Meticillin-resistant Staphylococcus aureus was isolated on blood cultures. The hospital course was complicated by massive haemoptysis and pulmonary aspiration necessitating mechanical ventilation. The patient subsequently made a complete recovery.

Conclusion

Lemierre's syndrome, although rare, is a potentially lethal but treatable complication of head and neck sepsis. Early clinical recognition of Lemierre's syndrome and appropriate antibiotic treatment can be life-saving. One should consider the possibility of community-acquired meticillin-resistant Staphylococcus aureus infection in patients with suspected Lemierre's syndrome.
Soft Tissue Sarcomas of Childhood and Adolescence: The Prognostic Role of Tumor Size in Relation to Patient Body Size
Authors: Ferrari Andrea , Miceli Rosalba , Meazza Cristina , Zaffignani Elena , Gronchi Alessandro , Piva Luigi , Collini Paola , Podda Marta , Massimino Maura , Luksch Roberto , Cefalo Graziella , Terenziani Monica , Spreafico Filippo , Polastri Daniela , Fossati-Bellani Franca , Casanova Michela , Mariani Luigi
Published: December 2008

Purpose

Tumor size is a key prognostic variable for soft tissue sarcomas (STS), and a tumor diameter of 5 cm is generally used as a cutoff for risk grouping purposes. This study aimed to investigate the prognostic effect of tumor size on overall survival and whether such an effect was influenced by the patient's size, expressed as body-surface area (BSA), in a series of 553 pediatric patients with localized STS.

Patients and Methods

Multivariable Cox models were used in which the effect of tumor size was adjusted for patients age, tumor site, histologic subtype, and Intergroup Rhabdomyosarcoma Study grouping, and the interaction between size and BSA was included.

Results

Tumor size was confirmed as a significant prognostic factor. Interaction between size and BSA meant that, for a given tumor size, the mortality increased from the larger to the smaller BSA. Conversely, the mortality risk associated with a patient with a BSA of 1.75 m2 and a 5-cm tumor was the same as for a 0.6 m2 child with a 2.8-cm tumor.

Conclusion

Tumor and body size are jointly informative on outcome. The risk associated with a given tumor size is not the same in patients of different body size, so it may be wrong to use the same 5-cm cutoff for tumor size in risk stratification.
Analysis of Risk Factors for Outcomes After Unrelated Cord Blood Transplantation in Adults With Lymphoid Malignancies: A Study by the Eurocord-Netcord and Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Rodrigues Celso A. , Sanz Guillermo , Brunstein Claudio G. , Sanz Jaime , Wagner John E. , Renaud Marc , de Lima Marcos , Cairo Mitchell S. , Fürst Sabine , Rio Bernard , Dalley Christopher , Carreras Enric , Harousseau Jean-Luc , Mohty Mohamad , Taveira Denis , Dreger Peter , Sureda Anna , Gluckman Eliane , Rocha Vanderson
Published: December 2008

Purpose

To determine risk factors of umbilical cord blood transplantation (UCBT) for patients with lymphoid malignancies.

Patients and Methods

We evaluated 104 adult patients (median age, 41 years) who underwent unrelated donor UCBT for lymphoid malignancies. UCB grafts were two-antigen human leukocyte antigen–mismatched in 68%, and were composed of one (n = 78) or two (n = 26) units. Diagnoses were non-Hodgkin's lymphoma (NHL, n = 61), Hodgkin's lymphoma (HL, n = 29), and chronic lymphocytic leukemia (CLL, n = 14), with 87% having advanced disease and 60% having experienced failure with a prior autologous transplant. Sixty-four percent of patients received a reduced-intensity conditioning regimen and 46% low-dose total-body irradiation (TBI). Median follow-up was 18 months.

Results

Cumulative incidence of neutrophil engraftment was 84% by day 60, with greater engraftment in recipients of higher CD34+ kg/cell dose (P = .0004). CI of non–relapse-related mortality (NRM) was 28% at 1 year, with a lower risk in patients treated with low-dose total-body irradiation (TBI; P = .03). Cumulative incidence of relapse or progression was 31% at 1 year, with a lower risk in recipients of double-unit UCBT (P = .03). The probability of progression-free survival (PFS) was 40% at 1 year, with improved survival in those with chemosensitive disease (49% v 34%; P = .03), who received conditioning regimens containing low-dose TBI (60% v 23%; P = .001), and higher nucleated cell dose (49% v 21%; P = .009).

Conclusion

UCBT is a viable treatment for adults with advanced lymphoid malignancies. Chemosensitive disease, use of low-dose TBI, and higher cell dose were factors associated with significantly better outcome.
Phase II Study of an Outpatient Palliative Care Intervention in Patients With Metastatic Cancer
Authors: Follwell Matthew , Burman Debika , Le Lisa W. , Wakimoto Kristina , Seccareccia Dori , Bryson John , Rodin Gary , Zimmermann Camilla
Published: December 2008

Purpose

Although there is increasing advocacy for timely symptom control in patients with cancer, few studies have assessed outpatient palliative care clinics. This study assessed prospectively the efficacy of an Oncology Palliative Care Clinic (OPCC) in improving patient symptom distress and satisfaction.

Patients and Methods

Eligible patients were new referrals to an OPCC, had metastatic cancer, were at least 18 years old, and were well enough and able to speak and read English sufficiently to provide informed consent and complete questionnaires. Patients received a consultation by a palliative care team. The primary end points of symptom control and patient satisfaction were assessed using the Edmonton Symptom Assessment Scale (ESAS) and patient-adapted Family Satisfaction with Advanced Cancer Care (FAMCARE) scale at baseline, 1 week, and 1 month. Initial and follow-up scores were compared using paired t tests.

Results

Of 150 patients enrolled, 123 completed 1-week assessments, and 88 completed 4-week assessments. At baseline, the mean ESAS Distress Score (EDS) was 39.5. The mean improvement in EDS was 8.8 points (P < .0001) at 1 week and 7.0 points (P < .0001) at 1 month. Statistically significant improvements were observed for pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, dyspnea, insomnia, and constipation at 1 week (all P ≤ .005) and 1 month (all P ≤ .05). The mean improvement in FAMCARE score was 6.1 points (P < .0001) at 1 week and 5.0 points (P < .0001) at 1 month.

Conclusion

This phase II study demonstrates efficacy of an OPCC for improvement of symptom control and patient satisfaction with care. Randomized controlled trials are indicated to further evaluate the effectiveness of specialized outpatient palliative care.
Monitoring for Lack of Benefit: A Critical Component of a Randomized Clinical Trial
Authors: Freidlin Boris , Korn Edward L.
Published: December 2008

To balance patient interests against the need for acquiring evidence, ongoing randomized clinical trials are formally monitored for early convincing indication of benefit or lack of benefit. In lethal diseases like cancer, where new therapies are often toxic and may have limited preliminary efficacy data, monitoring for lack of benefit is particularly important. We review the complex nature of stopping a randomized trial for lack of benefit and argue that many cancer trials could be improved by a more aggressive approach to monitoring. On the other hand, we caution that some commonly used monitoring guidelines may result in stopping for lack of benefit even when a nontrivial beneficial effect is observed.
Randomized Phase II Trial of Concurrent Cisplatin-Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma
Authors: Hui Edwin P. , Ma Brigette B. , Leung Sing F. , King Ann D. , Mo Frankie , Kam Michael K. , Yu Brian K. , Chiu Samuel K. , Kwan Wing H. , Ho Rosalie , Chan Iris , Ahuja Anil T. , Zee Benny C. , Chan Anthony T.
Published: December 2008

Purpose

To compare the toxicities, tumor control, survival, and quality of life of nasopharyngeal cancer (NPC) patients treated with sequential neoadjuvant chemotherapy followed by concurrent cisplatin-radiotherapy (CRT) or CRT alone.

Patients and Methods

Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks for two cycles, followed by cisplatin 40 mg/m2/wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs.

Results

From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemotherapy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012).

Conclusion

Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted.
Association Between Estrogen Receptor-β Expression and Epidermal Growth Factor Receptor Mutation in the Postoperative Prognosis of Adenocarcinoma of the Lung
Authors: Nose Naohiro , Sugio Kenji , Oyama Tsunehiro , Nozoe Tadahiro , Uramoto Hidetaka , Iwata Teruo , Onitsuka Takamitsu , Yasumoto Kosei
Published: December 2008

Purpose

Adenocarcinoma of the lung unrelated to a smoking habit occurs more frequently in women than men, thus suggesting an association between female hormones and development of these tumors. The aim of this study was to elucidate the correlation between expression of estrogen receptor (ER) and clinicopathologic factors, including a mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and prognosis in adenocarcinoma of the lung.

Patients and Methods

This study evaluated 447 resected primary lung adenocarcinoma specimens. The expression of ERα and ERβ was evaluated with an immunohistochemical method. The EGFR mutation was evaluated with polymerase chain reaction.

Results

A strong cytoplasmic expression of ERα and nuclear expression of ERβ were detected in 49.4% and 48.5% of all patients, respectively. A strong nuclear expression of ERβ was independently associated with the EGFR mutations (odds ratio = 2.947; 95% CI, 1.97 to 4.57; P < .001) and good differentiation (odds ratio = 1.84; 95% CI, 1.21 to 2.80; P = .004) and was correlated with an increasing disease-free survival in patients with EGFR mutations (hazard ratio = 2.18; 95% CI, 1.18 to 4.06; P = .014). However, no prognostic significance was identified in patients without EGFR mutations. No clinicopathologic and/or prognostic significance of a strong expression of cytoplasmic ERα was found.

Conclusion

A strong nuclear expression of ERβ correlates with EGFR mutations, and its favorable prognostic significance was influenced by the EGFR mutations in adenocarcinoma of the lung.
BRCA Germline Mutations in Jewish Patients With Pancreatic Adenocarcinoma
Authors: Ferrone Cristina R. , Levine Douglas A. , Tang Laura H. , Allen Peter J. , Jarnagin William , Brennan Murray F. , Offit Kenneth , Robson Mark E.
Published: December 2008

Purpose

The prognostic significance of germline BRCA1 and BRCA2 mutations in Jewish patients with pancreatic adenocarcinoma (PAC) is unknown. Our objective was to define the prevalence of BRCA1 and BRCA2 in an unselected group of Jewish patients and to compare the clinical characteristics and overall survival (OS) of patients with resected BRCA mutation-associated PAC to PAC patients without mutations.

Patients and Methods

Jewish patients with PAC resected between January 1986 and January 2004 were identified. DNA was extracted from the archived material, anonymized, and genotyped for founder mutations in BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT). Standard two-sided statistical tests were utilized.

Results

Of the 187 Jewish patients who underwent resection for PAC, tissue was available for 145 patients. Eight subjects (5.5%) had a BRCA founder mutation (two with BRCA1 [1.3%], six with BRCA2 [4.1%]). The BRCA2 founder mutation was identified in 4.1% of patients with pancreatic adenocarcinoma compared with only 1.1% of cancer-free Washington, DC,–area controls (4.1% v 1.1%; P = .007; odds ratio, 3.85; 95% CI, 2.1 to 10.8). Patients with and without BRCA1 or BRCA2 mutations did not differ in age (mean, 66 v 73 years; P = .6) or other clinicopathologic features. OS was not significantly different (median, 6 v 16 months; P = .35). A previous cancer was reported by 24% (35 of 145) of patients with the most common sites being breast cancer (9 of 35; 74%) and prostate cancer (8 of 35; 23%).

Conclusion

Founder mutations for BRCA1 and BRCA2 were identified in 5.5% of Ashkenazi patients operated on for PAC. BRCA2 mutations were more prevalent than documented by population studies. Consistent with previous reports, BRCA2 mutations are associated with an increased risk of PAC.
New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy
Authors: Chan Stephen L. , Mo Frankie K.F. , Johnson Philip J. , Hui Edwin P. , Ma Brigette B.Y. , Ho Wing M. , Lam Kwok C. , Chan Anthony T.C. , Mok Tony S.K. , Yeo Winnie
Published: December 2008

Purpose

There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial α-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point.

Patients and Methods

Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival.

Results

Of 188 patients, 117 patients with elevated serum AFP (> 20 μg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival.

Conclusion

Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.
Real-time acquisition of fatigue crack images for monitoring crack-tip stress intensity variations within fatigue cycles
Authors: Yusof F , Withers P J
Published: December 2008

Digital images of fatigue crack behaviour have been acquired in real time at high cycle fatigue rates (77 Hz) using a high-speed camera at 1000 frames/s. Digital image correlation has then been used to determine the crack-tip position and stress intensity variations ( KI and KII) within selected cycles. This has been achieved for a pre-cracked aluminium compact tension (CT) specimen subjected to constant load amplitude fatigue crack cycling. The crack-tip displacement field has been determined at 14 points within each cycle. In this proof of concept study, despite noise in the inferred displacement fields, by least squares fitting the displacement field rather than the strain field to the Muskhelishvili's form crack-tip stress field, the crack-tip stress intensity inferred from the measured crack-tip displacement field was found to good accuracy (around 0.2 MPa m1/2). Furthermore, the observed sinusoidal variation was in excellent agreement with the nominal Δ K obtained from the applied fatigue amplitude confirming the accuracy of the method; a drift of around 0.42 MPa m1/2 was observed in Kmean from cycle to cycle. No evidence of closure was observed at low K. In principle this method permits the identification of crack-tip closure and crack growth, as well as the application of constant Δ Keff cycling, through intermittent monitoring throughout the duration of a fatigue test. The current method is well suited to more complex cases where crack closure, residual stresses, or more complex geometries mean that it is difficult to predict Δ Keff a priori and a number of potential applications of the method are identified.
A study on microstructural changes and mechanical properties in steel rods subjected to uniform and non-uniform cooling layout using a finite element analysis
Authors: Nobari A H , Serajzadeh S
Published: December 2008

This paper presents a mathematical model for prediction of temperature history, final microstructures, and transformation kinetics in steel rods subjected to non-uniform cooling conditions. To achieve this goal, a mathematical model based on two-dimensional finite element method is developed to solve the governing heat conduction equation with non-uniform boundary conditions. The additivity rule is coupled with the finite element analysis to assess the kinetics of austenite decomposition during continuous cooling. The effect of decarburization during heating stage is also considered in the model employing Fick's second equation. To verify the predictions, time—temperature histories during cooling of a high carbon steel under different conditions have been considered and microstructural studies have also been performed by means of optical and scanning electron microscopy. The predictions have been found to be in good agreement with the experimental data.
In vitro characterization of aortic flow using numerical simulation, phase-contrast magnetic resonance imaging, and particle tracking images
Authors: Yang A-S , Wen C-Y , Tseng L-Y
Published: December 2008

Thoracic aorta and its three branches at the aortic arch are the inceptive zones of the aortic dissection and atherosclerosis. Owing to the complicated aortic flow, the geneses of these highly fatal diseases are the abnormal pressures and shear stresses acting upon the vascular intima. Hence, it is important to determine the distributions of wall shear stress (WSS) and wall pressure to predict these aortic disorders. In this study, the phase-contrast magnetic resonance imaging (PC-MRI) method was used to obtain the true geometry of a normal human thoracic aorta, which can be converted into a transparent thoracic aorta model by the rapid prototyping technique. The thoracic aorta model is then used in the in vitro experiment and computations. Numerical calculations were performed using the computational fluid dynamic software ACE+® to determine the flow characteristics of the three-dimensional, steady, incompressible, and Newtonian fluid in the thoracic aorta model. The boundary conditions at the inlet and the outlet of the aortic flow were specified from the measured data in the in vitro experiment. The predictions were in reasonable agreement with the PC-MRI-measured velocity profiles in the sagittal plane of the thoracic aorta model. The predictions suggest the preferential development of the early aortic dissection and atherosclerosis in the areas of either maxima or minima of WSS and wall pressure.
Experimental and numerical studies of squeeze mode behaviour of magnetic fluid
Authors: Gstöttenbauer N , Kainz A , Manhartsgruber B , Scheidl R
Published: December 2008

Magneto-rheological (MR) fluids are suspensions of micron-sized ferromagnetic particles in a non-magnetic carrier fluid. The essential characteristic of MR fluid is the rapid and reversible transition from the state of a Newtonian-like fluid to the behaviour of a stiff semi-solid by applying a magnetic field of ∼0.1–0.4 T. This feature can be understood from the fact that the particles form chain-like structures aligned in the field direction. The MR fluid offers three modes of operation, namely the direct shear mode, the valve mode, and the squeeze mode. The latter is of particular interest due to its highly non-linear behaviour, which is still not fully understood and therefore expected to give rise to new industrial applications. A test rig for the exploration of the MR-fluid behaviour was designed for experimental purposes. The present article describes the results of measurements under sinusoidal loading modes. Special emphasis was posed on the dependence of the MR-fluid response with respect to parameter variations of the applied static magnetic field, the cyclic loading amplitude, and frequency values. Cavitation effects have been investigated and partially suppressed by pre-pressurizing the MR fluid, which enables a more thorough insight into particle chain disruption and segregation effects. Well-pronounced hysteresis loops are observed and exhibit characteristic kinks, which cannot be understood within the frame of elementary constitutive laws such as for Bingham fluids. To describe the squeeze mode phenomenon numerically, adequate constitutive laws were applied, checked numerically by utilizing finite-element simulations, and validated against experimental data. New perceptions attained so far provided reason to design an adaptive MR-fluid bearing in squeeze mode behaviour for industrial applications.
Development of a vaned-type novel air turbine
Authors: Singh B R , Singh O
Published: December 2008

Worldwide depletion of fossil fuel due to its greater utilization is causing a serious threat to the environment. This has drawn global attention to its conservation, and the search for an alternative to fossil fuel driven engines. Compressed air is a potential working fluid for generating shaft work, and it can be a viable alternative to run light motor vehicles with reasonably small inbuilt compressed air tanks. In this article, the details of the development of a small air turbine with vaned-type rotor are presented. The proposed air turbine has been developed, and is in the process of being tested. Results based on its testing are presented here.
Defect-free synthesis of Stephenson-III motion generators
Authors: Hwang W-M , Chen Y-J
Published: December 2008

The main purpose of this article is to present a method for the dimensional synthesis of Stephenson-III motion generators without order, circuit, and branch defects. Using the concepts of the coupler curve of a four-bar linkage, the accessible region of a dyad, and the geometric feature of dead-centre configurations, a procedure is proposed for identifying the different circuits and branches of a Stephenson-III mechanism. Using the characteristics of order, circuit, and branch defects, the constraint equations to avoid them are presented. An optimization approach is proposed for the dimensional synthesis of defect-free Stephenson-III motion generators. An example is given to demonstrate the feasibility of the proposed method.
Natural gas spark ignition engine efficiency and NOx emission improvement using extreme exhaust gas recirculation enabled by partial reforming
Authors: Hosseini V , Checkel M D , Neill W S
Published: December 2008

Natural-gas (NG), spark ignition (SI) engines have widespread application in the power generation and upstream oil and gas industries. The manufacturers of these engines are being challenged to meet increasingly stringent nitrogen oxide (NO x) emission regulations without sacrificing fuel conversion efficiency.

SI engines may be operated with air—fuel mixtures lean of stoichiometric to achieve higher thermal efficiency and to reduce NO x emissions. Compared with new combustion strategies such as homogeneous charge compression ignition, however, lean SI combustion suffers from a somewhat limited tolerability to mixture dilution and high cyclic variations. Alternatively, NO x emissions may be reduced by using exhaust gas recirculation (EGR) to dilute a stoichiometric air—fuel mixture. This paper investigates the application of reformer gas (RG) to enable a higher mixture dilution of an NG SI engine using EGR.

It was found that RG enrichment allows an increase in the EGR dilution of a stoichiometric NG—air mixture from 12 per cent to more than 35 per cent. The optimal level of RG enrichment directly compensates for the combustion phasing retardation effect of EGR. Increasing the RG fraction in the mixture beyond the optimal value adversely affected the combustion process and fuel conversion efficiency. The experimental data suggest that NO x emissions comparable with the forthcoming 2010 US Environmental Protection Agency heavy-duty diesel engine regulations may be achieved using EGR, RG enrichment, and a three-way catalytic converter (TWC).

An energy balance showed that there is the potential to increase the overall system fuel conversion efficiency slightly owing to a more optimized combustion process after taking into account the energy losses associated with fuel reforming. The approach of EGR, fuel reforming, and a TWC is suitable for retrofits because it can be accomplished without modifying the engine geometry.
Dynamic analysis of an automobile floorpan using a hybrid approach of the finite element method and statistical energy analysis
Authors: Sui F , Moron P , Ichchou M , Jezequel L
Published: December 2008

An application of a hybrid approach of the finite element method (FEM) and statistical energy analysis (SEA) to a floorpan is presented. Modal analysis and frequency responses are implemented by FEM. The coupling loss factors employed in SEA are derived from the energy coefficient matrix based on FEM results. Appropriate substructuring configurations are investigated in an attempt to prevent the occurrence of negative and indirect coupling loss factors. Cross-examination analysis of various numbers of subsystems and damping levels are performed in order to assess different energy models. The issue of uncertainty in the high-frequency structural dynamics is also taken into account using Monte Carlo numerical calculations. The results of the hybrid approach are in good agreement with Monte Carlo simulations.
Structural optimization of the automobile frontal structure for pedestrian protection and the low-speed impact test
Authors: Shin M-K , Yi S-I , Kwon O-T , Park G-J
Published: December 2008

A variety of regulations are involved in the design of an automobile frontal structure. The regulations are pedestrian protection, the Federal Motor Vehicle Safety Standard (FMVSS) part 581 bumper test, and the Research Council for Automobile Repairs (RCAR) test. The frontal structure consists of the bumper system and a crash box that connects the bumper system and the main body. The detailed design of the bumper system is performed to meet two conditions: first, regulation for pedestrian protection (lower-legform impact test); second, FMVSS part 581. In the two regulations, the stiffness requirements of the bumper system conflict with each other. In order to meet lower leg protection, a relatively soft bumper system is required, while a relatively stiff system is typically needed to manage the pendulum impact. A new bumper system is proposed by adding new components and is analysed by using the non-linear finite element method. An optimization problem is formulated to incorporate the analysis results. Each regulation is considered as a constraint from a loading condition, and two loading conditions are used. Response surface approximation optimization is utilized to solve the formulated problem. RCAR requires reduction in the repair cost when an accident happens. The repair cost in a low-speed crash could be reduced by using an energy-absorbing structure such as the crash box. The crash box is analysed by using the non-linear finite element method. An optimization problem for the crash box is formulated to incorporate the analysis results. Discrete design using orthogonal arrays is utilized to solve the formulated problem in a discrete space.
Experimental study on the effects of mixture homogeneity on stratified-charge compression ignition combustion
Authors: Lu X-C , Ji L-B , Ma J-J , Huang C , Huang Z
Published: December 2008

In this paper, an investigation of the n-heptane stratified-charge compression ignition (SCCI) combustion on a single-cylinder engine using port fuel injection combined with in-cylinder direct injection is reported. The effects of mixture homogeneity, overall equivalence ratio, and fuel delivery advance angle of directly injected fuel on the SCCI combustion characteristics and emissions were evaluated. The experimental results revealed that the heat release curve of SCCI combustion exhibited a three-stage combustion mode, which includes low-temperature reaction (LTR), high-temperature reaction (HTR), and diffusion burn. The operating ranges can be significantly broadened by mixture stratification, owing to the smooth heat release. As the mixture homogeneity increases, the peak value of the heat release in the HTR increased but the maximum heat release in the third stage decreased. For a fixed overall equivalence ratio, with an increase in the mixture homogeneity, the nitrogen oxide (NO x) emissions from SCCI combustion started to decrease initially and attained the lowest level, but carbon monoxide (CO) emissions increased initially and achieved the highest level. Once the mixture homogeneity further increased, NO x emissions began to increase but CO emission decreased. Compared with the traditional direct-injection compression ignition combustion mode, NO x emissions from SCCI combustion can be reduced markedly. Also, hydrocarbon emissions from SCCI combustion were much lower than from neat homogeneous charge compression ignition combustion. The fuel delivery advance angle also had an important influence on SCCI combustion and the emissions. In particular, NO x emissions can be further significantly reduced using the late fuel injection strategy.
Analysis of stiffness and elastic deformation for a four-degree-of-freedom 4SPS + SP parallel manipulator with a SP passive constrained leg
Authors: Lu Y , Hu B , Yu J
Published: December 2008

The total stiffness matrix and elastic deformation of a four-degree-of-freedom (4-dof) four-spherical joint—active prismatic joint—spherical joint plus spherical joint—prismatic joint (4SPS + SP) parallel kinematic machine (PKM) with a passive constrained leg are studied systematically. First, the workspace of this PKM is constructed, and the poses of the active/constrained forces are determined. Second, based on the poses of active/constrained forces, the formulae are derived for solving the kinematics/statics, and some singularities of this PKM are determined. Third, a stiffness matrix of four spherical joint—active prismatic joint—spherical joint (SPS) active legs and one spherical joint—prismatic joint (SP) passive constrained leg is established. Finally, a total stiffness matrix and the elastic deformation of this PKM are solved and analysed based on the kinematics/statics formulae, the stiffness matrix of legs, and the principle of virtual work.
Modelling N- and W-shaped hazard rate functions without mixing distributions
Authors: Bebbington M , Lai C D , Murthy D N P , Zitikis R
Published: December 2008

The presence of non-conforming components instead of, or in addition to, the usual assembly errors results in N- or W-shaped hazard rate (HR) functions rather than the usual bathtub (i.e. U-shaped) ones. Although there have been numerous models for bathtub-shaped HR functions, N- and W-shaped HR functions are usually modelled using mixtures of two or more distributions. While this approach does sometimes lead to tidy interpretation, there can be a degree of overparameterization, with consequent problems in stability and fitting. For this reason, the present paper revisits the natural approach of modelling N- and W-shaped HR functions using polynomial functions of degree three or four. Although the non-negativity of the hazard rate function becomes non-trivial, this ensures a minimal number of parameters. The polynomial approach also allows the use of a parametric model without imposing a particular shape of hazard rate function on the data, which usually requires a non-parametric approach. The possible hazard rate shapes obtainable are characterized, and detailed formulae for local minima and maxima of the functions provided. The performance of the models is compared to that of several generalizations of the Weibull distribution, with promising results.
Flow cytometer with mass spectrometer detection for massively multiplexed single-cell biomarker assay
Authors: Tanner Scott D. , Bandura Dmitry R. , Ornatsky Olga , Baranov Vladimir I. , Nitz Mark , Winnik M. A.
Published: December 2008

This paper describes the development and application of new metal-tagging reagents and a novel mass spectrometer (MS) detector for a flow cytometer that enables highly multiplexed measurement of many biomarkers in individual cells. A new class of tagging reagents, based on an acrylic polymer backbone that incorporates a reproducible number of lanthanide elements, has been developed. When linked to antibodies that specifically recognize target proteins of interest, determination of the tag elements is diagnostic for the presence and quantification of the antigen. The use of enriched stable isotope tags provides the opportunity for multiparametric assay. The new instrument uses inductively coupled plasma (ICP) to vaporize, atomize, and ionize individual cells that have been probed using the metal-labeled antibodies. The elemental composition, specifically of the metal tags, is recorded simultaneously using a time-of-flight (TOF)-MS that has been specifically designed for high-speed analysis during the short transient corresponding to the individual cell event. The detector provides for well-resolved atomic fingerprints of many elemental and isotopic tags, with little overlap of neighboring signals (high abundance sensitivity) and wide dynamic range both for a single antigen and between antigens.
Zinc proteomics and the annotation of the human zinc proteome
Authors: Maret Wolfgang
Published: December 2008

Sequence databases can be searched for homologies of zinc coordination motifs with characteristic ligand signatures. Ensuing predictions that 3-10 % of the human genes encodes zinc proteins are most remarkable. But they seem conservative when considering that database mining cannot discover new signatures or coordination environments that employ nonsequential binding of ligands and sulfur-ligand bridges. Predictions also fall short for zinc/protein interactions at protein interfaces and for inhibitory zinc sites. Zinc ions transiently target proteins that are not known to be zinc proteins, adding a hitherto unrecognized dimension to the human zinc proteome. Predicted zinc sites need to be verified experimentally. The metal can be absent or sites may bind metal ions other than zinc because protein coordination environments do not have absolute specificity for zinc. The metaphor of the "galvanization of biology" continues to gain prominence in terms of the sheer number of approximately 3000 human zinc proteins and their annotation with new functions. Clearly, description of zinc proteomes cannot be pursued solely in silico and requires zinc proteomics, an integrated scientific approach. Progress hinges on a combination of bioinformatics, biology, and significantly, analytical and structural chemistry.
"Platinum on the road": Interactions of antitumoral cisplatin with proteins
Authors: Arnesano Fabio , Natile Giovanni
Published: December 2008

When the antitumor activity of cisplatin was discovered, no one would have thought of the existence of specific proteins able to transport Pt across the cell membrane or to specifically recognize DNA modified by this drug. However, such proteins do exist and, furthermore, are specific for the Pt substrate considered. It follows that proteins are deeply involved in managing the biological activity of cisplatin. It is expected that, after the first 20 years in which most of the efforts were devoted to understanding its mode of interaction with DNA and consequent structural and functional alterations, the role of proteins will be more deeply scavenged. How cisplatin can survive the attack of the many platinophiles present in the extracellular and intracellular media is the issue addressed in this article. Significantly, differences are observed between cisplatin, carboplatin, and oxaliplatin.