bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of two goniometric methods of measuring active inversion and eversion range of motion at the ankle
Authors: Menadue Collette , Raymond Jacqueline , Kilbreath Sharon L , Refshauge Kathryn M , Adams Roger
Published: July 2006

Background

Active inversion and eversion ankle range of motion (ROM) is widely used to evaluate treatment effect, however the error associated with the available measurement protocols is unknown. This study aimed to establish the reliability of goniometry as used in clinical practice.

Methods

30 subjects (60 ankles) with a wide variety of ankle conditions participated in this study. Three observers, with different skill levels, measured active inversion and eversion ankle ROM three times on each of two days. Measurements were performed with subjects positioned (a) sitting and (b) prone. Intra-class correlation coefficients (ICC[2,1]) were calculated to determine intra- and inter-observer reliability.

Results

Within session intra-observer reliability ranged from ICC[2,1] 0.82 to 0.96 and between session intra-observer reliability ranged from ICC[2,1] 0.42 to 0.80. Reliability was similar for the sitting and the prone positions, however, between sessions, inversion measurements were more reliable than eversion measurements. Within session inter-observer measurements in sitting were more reliable than in prone and inversion measurements were more reliable than eversion measurements.

Conclusion

Our findings show that ankle inversion and eversion ROM can be measured with high to very high reliability by the same observer within sessions and with low to moderate reliability by different observers within a session. The reliability of measures made by the same observer between sessions varies depending on the direction, being low to moderate for eversion measurements and moderate to high for inversion measurements in both positions.
High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia
Authors: Schunk Mirjam , Kumma Wondimagegn P , Miranda Isabel Barreto , Osman Maha E , Roewer Susanne , Alano Abraham , Löscher Thomas , Bienzle Ulrich , Mockenhaupt Frank P
Published: July 2006

Background

In Ethiopia, malaria is caused by both Plasmodium falciparum and Plasmodium vivax. Drug resistance of P. falciparum to sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) is frequent and intense in some areas.

Methods

In 100 patients with uncomplicated malaria from Dilla, southern Ethiopia, P. falciparum dhfr and dhps mutations as well as P. vivax dhfr polymorphisms associated with resistance to SP and P. falciparum pfcrt and pfmdr1 mutations conferring CQ resistance were assessed.

Results

P. falciparum and P. vivax were observed in 69% and 31% of the patients, respectively. Pfdhfr triple mutations and pfdhfr/pfdhps quintuple mutations occurred in 87% and 86% of P. falciparum isolates, respectively. Pfcrt T76 was seen in all and pfmdr1 Y86 in 81% of P. falciparum. The P. vivax dhfr core mutations N117 and R58 were present in 94% and 74%, respectively.

Conclusion

These data point to an extraordinarily high frequency of drug-resistance mutations in both P. falciparum and P. vivax in southern Ethiopia, and strongly support that both SP and CQ are inadequate drugs for this region.
Perforated gastric carcinoma: a report of 10 cases and review of the literature
Authors: Roviello Franco , Rossi Simone , Marrelli Daniele , De Manzoni Giovanni , Pedrazzani Corrado , Morgagni Paolo , Corso Giovanni , Pinto Enrico
Published: July 2006

Background

Perforation is a rare complication of gastric carcinoma, accounting for less than 1% of all gastric cancer cases. The aim of the present study is to evaluate the prognostic value of perforation and to point out the surgical treatment options.

Methods

A total of 10 patients with perforated gastric carcinoma were retrospectively reviewed among 2564 consecutive cases of gastric cancer operated in three Centers belonging to the Italian Research Group for Gastric Cancer. The clinicopathological features including tumor stage and survival were analyzed and compared to literature data.

Results

Incidence rate was 0.39%. All patients underwent emergency surgery, being performed gastrectomy in 6 patients (mortality 17%) and repair surgery in 4 patients (mortality 75%). The survival of patients was related to the stage of the disease, with 2 long-survival cases.

Conclusion

Perforation usually occurs in advanced stages of gastric cancer; nevertheless surgeons should not be always discouraged from a radical treatment of perforated gastric cancer, since perforation even occurs in early stages and seems not to be a negative prognostic factor itself. When possible, emergency gastrectomy should be performed, leaving repair surgery for unresectable tumors. A two-stage treatment is a good treatment option for frail patients with resectable tumors.
Breast Cancer–Specific mRNA Transcripts Presence in Peripheral Blood After Adjuvant Chemotherapy Predicts Poor Survival Among High-Risk Breast Cancer Patients Treated With High-Dose Chemotherapy With Peripheral Blood Stem Cell Support
Authors: Quintela-Fandino Miguel , López Joaquín Martínez , Hitt Ricardo , Gamarra Soledad , Jimeno Antonio , Ayala Rosa , Hornedo Javier , Guzman Cecilia , Gilsanz Florinda , Cortés-Funes Hernán
Published: July 2006

Purpose

To study the prognostic significance of the presence of breast cancer–specific mRNA transcripts in peripheral blood (PB), defined by serial analysis of gene expression, in high-risk breast cancer (HRBC) patients undergoing high-dose chemotherapy after receiving adjuvant chemotherapy.

Methods

From 1994 to 2000, 84 HRBC patients (median age, 44 years; > 10 nodes; 74%) received adjuvant chemotherapy (fluorouracil, epirubicin, and cyclophosphamide for six cycles [83%] or doxorubicin and cyclophosphamide followed by paclitaxel) before undergoing one course of cyclophosphamide plus thiotepa plus carboplatin (STAMP V). Radiotherapy or hormone therapy was administered whenever indicated. Aliquots of apheresis-mononuclear blood cells were frozen from each patient. mRNA was isolated using an automatic nucleic acid extractor based on the magnetic beads technology; reverse transcription was performed using random hexamers. Cytokeratin 19, HER-2, P1B, PS2, and EGP2 transcripts were quantified to B-glucuronidase by real-time polymerase chain reaction (RT-PCR) using a linear DNA probe marked with a quencher and reporter fluorophores used in RT-PCR. Presence of PB micrometastases, estrogen receptor and progesterone receptor status, tumor size, age, tumor grade, number of nodes affected, and treatment with paclitaxel were included in the statistical analysis.

Results

Median follow-up was 68.3 months (range, 6 months to 103 months). Forty-seven relapses (56%) and 35 deaths (41.7%) were registered. Both tumor size and presence of micrometastases reached statistical significance according to the Cox multivariate model. Relapse hazard ratio (HR) for those patients with PB micrometastases was 269% (P = .006); death HR, 300% (P = .011). Time relapse was 53 months longer for patients without micrometastases: 31.3 v 84.2 months (P = .021).

Conclusion

PB micrometastases presence after adjuvant chemotherapy predicts both relapse and death more powerful than classical factors in HRBC patients undergoing high-dose chemotherapy. Micrometastases search using a gene panel appears to be a more accurate procedure than classical approaches involving only one or two genes.
Phase III Trial of Fluorouracil-Based Chemotherapy Regimens Plus Radiotherapy in Postoperative Adjuvant Rectal Cancer: GI INT 0144
Authors: Smalley Stephen R. , Benedetti Jacqueline K. , Williamson Stephen K. , Robertson John M. , Estes Norman C. , Maher Tracy , Fisher Barbara , Rich Tyvin A. , Martenson James A. , Kugler John W. , Benson Al B. , Haller Daniel G. , Mayer Robert J. , Atkins James N. , Cripps Christine , Pedersen John , Periman Phillip O. , Tanaka Michael S. , Leichman Cynthia G. , Macdonald John S.
Published: July 2006

Purpose

Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens.

Patients and Methods

After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery.

Results

Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3.

Conclusion

All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.
Risk Factors Before Autologous Stem-Cell Transplantation for Lymphoma Predict for Secondary Myelodysplasia and Acute Myelogenous Leukemia
Authors: Kalaycio Matt , Rybicki Lisa , Pohlman Brad , Sobecks Ronald , Andresen Steven , Kuczkowski Elizabeth , Bolwell Brian
Published: July 2006

Purpose

The risk factors for treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (AML) after autologous stem-cell transplantation (ASCT) are similar to those that increase the risk of difficult stem-cell harvests. We reviewed our experience in 526 patients with lymphoma treated by ASCT to determine whether difficult stem-cell harvests predict for an increased risk of t-MDS/AML.

Patients and Methods

Autologous peripheral stem cells were initially mobilized with granulocyte colony-stimulating factor (G-CSF; or granulocyte-macrophage colony-stimulating factor) alone (n = 334), etoposide and G-CSF (n = 166), or cyclophosphamide and G-CSF with or without etoposide (n = 26). Difficult harvests were those that required more than 5 days to collect enough stem cells and those that required additional attempts with etoposide and/or cyclophosphamide plus G-CSF (n = 52). All patients were then treated with high-dose chemotherapy alone and observed for outcome.

Results

With a median follow-up time for surviving patients of 69 months, 20 patients developed t-MDS/AML, for an actuarial incidence of 6.8% at 10 years. Pretransplantation characteristics, including age, diagnosis of non-Hodgkin's lymphoma or Hodgkin's disease, bone marrow involvement, prior radiation therapy, prior exposure to chemotherapy, lactate dehydrogenase at the time of ASCT, disease status, and method of stem-cell mobilization, were then analyzed with respect to the subsequent development of t-MDS/AML. By multivariable analysis, prior exposure to radiation therapy, four or more chemotherapy regimens, and more than 5 days of apheresis needed to harvest enough stem cells were identified as independent risk factors for t-MDS/AML. Bootstrap analysis confirmed these results.

Conclusion

These results suggest that identifiable pretransplantation factors predict for t-MDS/AML after ASCT.
Phase III Study of Docetaxel Compared With Vinorelbine in Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904)
Authors: Kudoh Shinzoh , Takeda Koji , Nakagawa Kazuhiko , Takada Minoru , Katakami Nobuyuki , Matsui Kaoru , Shinkai Tetsu , Sawa Toshiyuki , Goto Isao , Semba Hiroshi , Seto Takashi , Ando Masahiko , Satoh Taroh , Yoshimura Naruo , Negoro Shunichi , Fukuoka Masahiro
Published: July 2006

Purpose

Docetaxel has shown activity in elderly patients with advanced non–small-cell lung cancer (NSCLC). This randomized phase III trial evaluated the efficacy and safety of docetaxel versus vinorelbine (the current standard treatment) in elderly patients.

Patients and Methods

Chemotherapy-naïve patients age 70 years or older with stage IIIB/IV NSCLC and performance status 2 or lower were eligible. Patients randomly received docetaxel 60 mg/m2 (day 1) or vinorelbine 25 mg/m2 (days 1 and 8) every 21 days for four cycles. The primary end point was overall survival. Overall disease-related symptom improvement was assessed using an eight-item questionnaire.

Results

In total, 182 patients were enrolled. Median age was 76 years (range, 70 years to 86 years). There was no statistical difference in median overall survival with docetaxel versus vinorelbine (14.3 months v 9.9 months; hazard ratio, 0.780; 95% CI, 0.561 to 1.085; P = .138). There was a significant difference in median progression-free survival (5.5 months v 3.1 months; P < .001). Response rates were also significantly improved with docetaxel versus vinorelbine (22.7% v 9.9%; P = .019). The most common grade 3 to 4 toxicities were neutropenia (82.9% for docetaxel; 69.2% for vinorelbine; P = .031) and leukopenia (58.0% for docetaxel; 51.7% for vinorelbine). Other toxicities were mild and generally well tolerated. Docetaxel improved overall disease-related symptoms over vinorelbine (odds ratio, 1.86; 95% CI, 1.09 to 3.20).

Conclusion

Docetaxel improved progression-free survival, response rate, and disease-related symptoms versus vinorelbine. Overall survival was not statistically significantly improved at this time. Docetaxel monotherapy may be considered as an option in the standard treatment of elderly patients with advanced NSCLC.
Phase II Trial of Tipifarnib in Patients With Recurrent Malignant Glioma Either Receiving or Not Receiving Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study
Authors: Cloughesy Timothy F. , Wen Patrick Y. , Robins H. Ian , Chang Susan M. , Groves Morris D. , Fink Karen L. , Junck Larry , Schiff David , Abrey Lauren , Gilbert Mark R. , Lieberman Frank , Kuhn John , DeAngelis Lisa M. , Mehta Minesh , Raizer Jeff J. , Yung W.K. Alfred , Aldape Ken , Wright John , Lamborn Kathleen R. , Prados Michael D.
Published: July 2006

Purpose

A phase II study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on EIAEDs. The population included 67 patients with glioblastoma multiforme (GBM) and an exploratory group of 22 patients with anaplastic glioma (AG).

Patients and Methods

Patients received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED and EIAED patients, respectively). All patients were assessable for efficacy and safety.

Results

Two AG patients (9.1%) and eight GBM patients (11.9%) had progression-free survival (PFS) more than 6 months. Among the latter eight GBM patients, six of 36 patients (16.7%; 95% CI, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% CI, 1% to 20%) were receiving EIAEDs. Four patients had partial responses in group A GBM and one patient had a partial response group B GBM. An exploratory comparison of PFS between GBM groups A and B was statistically significant (P = .01). Patients not receiving EIAEDs had a higher incidence and increased severity of hematologic events. However, the incidence and severity of rash (the previously determined dose-limiting toxicity in patients receiving EIAEDs) seemed similar in EIAED and non-EIAED subgroups.

Conclusion

Tipifarnib (300 mg bid for 21 days every 4 weeks) shows modest evidence of activity in patients with recurrent GBM who are not receiving EIAEDs and is generally well tolerated in this population.
Combined Deletion of Y1, Y2, and Y4 Receptors Prevents Hypothalamic Neuropeptide Y Overexpression-Induced Hyperinsulinemia despite Persistence of Hyperphagia and Obesity
Authors: Lin En-Ju D. , Sainsbury Amanda , Lee Nicola J. , Boey Dana , Couzens Michelle , Enriquez Ronaldo , Slack Katy , Bland Ross , During Matthew J. , Herzog Herbert
Published: July 2006

Neuropeptide Y (NPY) is a key regulator of energy homeostasis and is implicated in the development of obesity and type 2 diabetes. Whereas it is known that hypothalamic administration of exogenous NPY peptides leads to increased body weight gain, hyperphagia, and many hormonal and metabolic changes characteristic of an obesity syndrome, the Y receptor(s) mediating these effects is disputed and unclear. To investigate the role of different Y receptors in the NPY-induced obesity syndrome, we used recombinant adeno-associated viral vector to overexpress NPY in mice deficient of selective single or multiple Y receptors (including Y1, Y2, and Y4). Results from this study demonstrated that long-term hypothalamic overexpression of NPY lead to marked hyperphagia, hypogonadism, body weight gain, enhanced adipose tissue accumulation, hyperinsulinemia, and other hormonal changes characteristic of an obesity syndrome. NPY-induced hyperphagia, hypogonadism, and obesity syndrome persisted in all genotypes studied (Y1−/−, Y2−/−, Y2Y4−/−, and Y1Y2Y4−/− mice). However, triple deletion of Y1, Y2, and Y4 receptors prevented NPY-induced hyperinsulinemia. These findings suggest that Y1, Y2, and Y4 receptors under this condition are not crucially involved in NPY’s hyperphagic, hypogonadal, and obesogenic effects, but they are responsible for the central regulation of circulating insulin levels by NPY.
Inhibition of Prostate Cancer Cell Growth by Human Secreted PDZ Domain-Containing Protein 2, a Potential Autocrine Prostate Tumor Suppressor
Authors: Tam C. W. , Cheng A. S. , Ma R. Y. M. , Yao K.-M. , Shiu S. Y. W.
Published: July 2006

A possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and secretion of sPDZD2 in cancerous DU145, PC-3, 22Rv1, LNCaP, and immortalized RWPE-1 prostate epithelial cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, and RWPE-1 cells via the caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which was abrogated by treatment with exogenous recombinant sPDZD2. Whereas sPDZD2-induced antiproliferation in DU145, PC-3, and 22Rv1 cells, it induced apoptosis in LNCaP cells. The data suggest that endogenous sPDZD2, produced by caspase-3-mediated cleavage from PDZD2, may function as a novel autocrine growth suppressor for human prostate cancer cells. The antiproliferative effect of sPDZD2 was apparently mediated through slowing the entry of DU145, PC-3, and 22Rv1 cells into the S phase of the cell cycle. In DU145 cells, this can be attributed to stimulated p53 and p21CIP1/WAF1 expression by sPDZD2. On the other hand, the apoptotic effect of sPDZD2 on LNCaP cells was apparently mediated via p53-independent Bad stimulation. Together our results indicate the presence of p53-dependent and p53-independent PDZD2/sPDZD2 autocrine growth suppressive signaling pathways in human prostate cancer cells and suggest a novel therapeutic approach of harnessing the latent tumor-suppressive potential of an endogenous autocrine signaling protein like sPDZD2 to inhibit prostate cancer growth.
Inhibition of Insulin-Stimulated Glycogen Synthesis by 5-Aminoimidasole-4-Carboxamide-1-β-d-Ribofuranoside-Induced Adenosine 5′-Monophosphate-Activated Protein Kinase Activation: Interactions with Akt, Glycogen Synthase Kinase 3-3α/β, and Glycogen Synthase in Isolated Rat Soleus Muscle
Authors: Fediuc S. , Gaidhu M. P. , Ceddia R. B.
Published: July 2006

The aim of this study was to investigate the effects of 5-aminoimidasole-4-carboxamide-1-β-d-ribofuranoside (AICAR)-induced AMP-activated protein kinase activation on glycogen metabolism in soleus (slow twitch, oxidative) and epitrochlearis (fast twitch, glycolytic) skeletal muscles. Isolated soleus and epitrochlearis muscles were incubated in the absence or presence of insulin (100 nm), AICAR (2 mm), and AICAR plus insulin. In soleus muscles exposed to insulin, glycogen synthesis and glycogen content increased 6.4- and 1.3-fold, respectively. AICAR treatment significantly suppressed (∼60%) insulin-stimulated glycogen synthesis and completely prevented the increase in glycogen content induced by insulin. AICAR did not affect either basal or insulin-stimulated glucose uptake but significantly increased insulin-stimulated (∼20%) lactate production in soleus muscles. Interestingly, basal glucose uptake was significantly increased (∼1.4-fold) in the epitrochlearis muscle, even though neither basal nor insulin-stimulated rates of glycogen synthesis, glycogen content, and lactate production were affected by AICAR. We also report the novel evidence that AICAR markedly reduced insulin-induced Akt-Thr308 phosphorylation after 15 and 30 min exposure to insulin, which coincided with a marked reduction in glycogen synthase kinase 3 (GSK)-3α/β phosphorylation. Importantly, phosphorylation of glycogen synthase was increased by AICAR treatment 45 min after insulin stimulation. Our results indicate that AICAR-induced AMP-activated protein kinase activation caused a time-dependent reduction in Akt308 phosphorylation, activation of glycogen synthase kinase-3α/β, and the inactivation of glycogen synthase, which are compatible with the acute reduction in insulin-stimulated glycogen synthesis in oxidative but not glycolytic skeletal muscles.
Comparison of Superior Mesenteric Versus Jugular Venous Infusions of Insulin in Streptozotocin-Diabetic Rats on the Choice of Caloric Intake, Body Weight, and Fat Stores
Authors: Warne James P. , Horneman Hart F. , Wick Elizabeth C. , Bhargava Aditi , Pecoraro Norman C. , Ginsberg Abigail B. , Akana Susan F. , Dallman Mary F.
Published: July 2006

Corticosterone (B) increases and insulin decreases food intake. However, in streptozotocin (STZ)-diabetic rats with high B, low insulin replacement promotes lard intake. To test the role of the liver on this, rats were given STZ and infused with insulin or vehicle into either the superior mesenteric or right jugular vein. Controls were nondiabetic; all rats were treated with high B. After 5 d, all rats were offered lard, 32% sucrose, chow, and water ad libitum until d 10. Diabetes exacerbated body weight loss from high B; this was prevented by insulin into the jugular, but not superior mesenteric, vein. Without insulin, STZ groups essentially consumed only chow; controls increased caloric intake about equally from the three sources. Insulin into both sites reduced chow and increased lard intake. Although circulating insulin was increased only by jugular infusion, plasma glucose and liver glycogen were similar after insulin into both sites. Fat depot weights differed: sc fat was heavier after jugular and mesenteric fat was heavier after mesenteric insulin infusions. We conclude that there are important site-specific effects of insulin in regulating the choice of, but not total, caloric intake, body weight, and fat storage in diabetic rats with high B. Furthermore, lard intake might be regulated by an insulin-derived, liver-mediated signal because superior mesenteric insulin infusion had similar effects on lard intake to jugular infusion but did not result in elevated circulating insulin levels likely associated with liver insulin removal.
Origin and Identity of Adrenocortical Tumors in Inhibin Knockout Mice: Implications for Cellular Plasticity in the Adrenal Cortex
Authors: Looyenga Brendan D. , Hammer Gary D.
Published: July 2006

Inhibin knockout (Inha−/−) mice develop gonadal sex-cord tumors and—when gonadectomized—adrenocortical tumors. Previous reports demonstrated that adrenocortical tumors from Inha−/− mice produce estrogen and depend on gonadotropin signaling for initiation. Here we show that, in addition to producing estrogen, the adrenocortical tumors display a global change in cellular identity, composed of two unique cell types expressing differing arrays of genes normally restricted to theca and granulosa cells of the ovary. Many of these genes are also induced in wild-type adrenals after gonadectomy or upon chronic gonadotropin stimulation, suggesting that the adrenal cortex normally contains a population of pluripotent cells that can be driven toward an adrenal or gonadal identity given the appropriate pituitary stimuli. A central feature of this altered cellular identity is the switch from predominant expression of Gata6 (endogenous to the adrenal cortex) to Gata4, which defines cellular identity in the ovary. We show that stable transfection of Gata4 in cultured adrenocortical cells is sufficient to activate ovarian-specific genes of both theca and granulose lineages. Spatial analysis of Gata4 expression reveals a distinct pattern of localization to the supcapsular region of the adrenal, which contains undifferentiated progenitor cells that continuously populate the adrenocortical zones. Although both wild-type and Inha−/− mice display this pattern, only Inha−/− mice produce tumors composed of these Gata4-positive cells. These data suggest that Inha−/− adrenocortical tumors cells are derived from pluripotent adrenocortical progenitor cells that adopt a gonadal fate due to the convergent loss of inhibin and chronic exposure to elevated gonadotropins.
Prediction of Surface Quality from Ball-Nose Milling in High-Speed Machining Applications
Authors: Liu N , Loftus M
Published: July 2006

Many of the finishing operations in the manufacture of dies and moulds are dependent on ball-nose milling cutters to produce the required geometry and surface quality. These cutters (high cost, carbide coated) work best in situations where the load on the cutter is constant and rapid changes in direction are kept to a minimum. The majority of computer aided manufacturing (CAM) systems provide a number of alternative machining strategies to support this approach, but they do not provide an accurate prediction of the surface quality in the finished product. This paper outlines a predictive theory for the surface quality. The ball-nose cutting mechanism has been modelled and simulated to generate the surface topography expected in the actual operation. The results match those from the experimental machining trials and enable the prediction and determination of the surface quality in other applications prior to the machining operations.
Measurements and Evaluations of Drilling Burr Profile
Authors: Nakao Y , Watanabe Y
Published: July 2006

A newly developed system for measuring the profiles of the height and thickness of drilling burrs using image-processing techniques is presented. The measurement accuracy of this system was verified through simulations and experimental studies. The verification tests showed that the measurement accuracy is approximately 50 μm. This system was also used for measuring irregular burr profiles, which tend to cause large dispersions in experimental results. In addition to the standard function (measuring the burr profiles), an additional function was integrated into the measurement software. The additional function can be used to evaluate the uniformity of the burr profiles and to remove the influence of irregular burrs from the measured original data. The effectiveness of these additional functions was also verified through experimental studies.
Computer Aided Process Planning, Strategy, and Models in the Aircraft Industry
Authors: Capponi V , Zirmi O , Brissaud D , Villeneuve F
Published: July 2006

Unlike computer aided design (CAD) and computer aided manufacturing (CAM) systems which have been used in industry for a long time, computer aided process planning (CAPP) systems are yet to be transferred from research laboratories to industry. Aircraft industries are trying to improve their performance by developing CAPP software, and the present study contributes to this effort. Aircraft parts are specific mainly because of their complex geometry, which generates many accessibility problems, and their thin shells, which generate machining deformation and vibration problems. New CAPP approaches have been specified and developed for aircraft structural parts. Machining features are defined as machining faces. The part is split up into a set of machining faces with accessibility, adjacency, and rigidity properties. New set-up strategies are defined. These highlight three particular features in the machining of such parts: the categorization, which is a strict guide as to how the part should be machined; the best-fit blank orientation relative to the part; and the potential machining directions of the part which are the main elements for decision making.
Proposed Methodology for Optimizing Grooving Operations of Ferrous Sintered Material
Authors: Deshayes L , Rigal J-F , Play D
Published: July 2006

Nowadays, powder metallurgy technology is increasingly used for the production of components with complex prismatic geometries. On account of the sintering process, machining operations have to be used for obtaining the final workpiece. Cutting operations are the limitation processes for sintered product owing to the weak machinability of sintered materials. Design has to consider such limitations early in the product development for reducing cost and enabling powder technology to compete with other technologies. This goal can be achieved only if cutting operations are well optimized through a unified methodology. In this paper, ‘couple workpiece-tool’ (CWT) methodology is used to optimize the machining of sintered steels. The study case used in this paper consists in determining optimal cutting conditions for an external grooving operation on sintered tooth sprockets on the basis of results obtained with continuous grooving operations. The influence of cutting parameters on machined surface and quality indices of the process, such as burr height, tool wear, and surface integrity, is studied. Results, based on experiments, are used to propose recommendations and new criteria to consider in CWT methodology for intermittent and continuous cutting of sintered steels.
Search Space Scaling in Genetic Algorithm-Based Inverse Analyses
Authors: Wood R L
Published: July 2006

Inverse problems arise at all levels of manufacturing organization through the need to estimate system parameters and optimize performance. In modelling the physics of various manufacturing processes, inverse analysis is primarily used to estimate boundary conditions at the part/machine interface. The quality of such estimates is influenced by the measurement process, the physics model, and the inverse analysis mechanism. Of the available mechanisms, genetic algorithms (GAs) are unusual because they do not rely on the use of sensitivity coefficients and they are easily integrated with direct models of process physics. Primary factors that influence GA performance are the topology of the search space and the way that this is sampled by the GA. Search space topology is dictated by comparison of the measured and calculated effects of the sought boundary conditions. Search space sampling is controlled by chosen chromosome structure and previous evolutionary progress. A method of dynamic search space scaling is discussed here, in which contractions of search space dimensions follow evolutionary progress and are triggered by changing population diversity within the GA. In comparison to evolution in a fixed search space, it is shown that dynamic search space scaling can be efficient in producing highly accurate estimates.
Geometrical Modelling of a Ball-End Finish Milling Process for a Surface Finish
Authors: Sriyotha P , Sahasrabudhe A , Yamazaki K , Mori M
Published: July 2006

Finish milling with a ball-end mill is a key process in manufacturing high-precision and complex workpieces such as dies and moulds. Due to the complexity of the milling process, it is difficult to observe experimentally the surface microcharacteristics such as the surface topography and roughness of machined workpieces real-time during machining. This necessitates simulation of the process. In this area, the existing related simulation researches focus mainly on scallop heights; few have presented a whole picture of the microcharacteristics of milled surfaces. A comprehensive simulation system has been developed for predicting the surface topographic features and roughness formed in the milling process, and the effect of machining parameters was studied. This paper focuses on the modelling method and theory adopted in the simulation system. The method to improve the calculation accuracy is discussed in detail. The approach to incorporate the effects of the cutting tool run-out and wear is also presented. Experiments are also carried out to verify the simulation results.
The Development of a Triple Ball Bar System for Calibration of CNC Machine Tools
Authors: Jywe Wenyuh , Liu Chien Hung , Lin Bor Jeng , Hsu Tung Hui
Published: July 2006

The accuracy of machine tools restricts the dimensional accuracy of parts processed thereon. It is, therefore, necessary to monitor the errors of machine tools constantly. Normally, it takes a long set-up time before one can observe the machine tool and monitor its errors. The cost of such delays is inevitably high. As for CNC, the conventional measurement system is capable of measuring one-dimensional signals, as a laser interferometer does, and two-dimensional signals, as a grid encoder does. Three-dimensional measurement techniques, however, are far from being well developed and are not yet well known. This paper proposes a triangulation method incorporating three built-in linear-scale ball bars that requires less set-up time and lower costs than the laser ball bar system, and is capable of acquiring three-dimensional signals with greater accuracy with the extension bars, so that large volumes can be checked.
Two-Dimensional Tool Design for Two-Dimensional Equilibrium Electrochemical Machining Die-Sinking Using a Numerical Method
Authors: McClennan J , Alder G , Sherlock A , Mill F , Clifton D
Published: July 2006

Electrochemical machining (ECM) can be defined as controlled electrolytic anodic erosion. ECM can machine hard alloys and metals with tools of softer metals, without affecting either workpiece microstructure or surface properties. There is no tool wear owing to a lack of tool/workpiece contact. The ECM medium between the tool and workpiece is electrically conductive, causing the finished workpiece geometry to vary from the tool and not to become a direct inverse of the tool shape. The characteristics of the workpiece material can also affect shape transfer, increasing the difficulty of designing and simulating ECM tools.

At present, ECM tool design in industry is a trial-and-error process that can be prohibitively time-consuming. Automated design and simulation procedures are, therefore, desirable.

This paper describes a computational approach to ECM tool design for two-dimensional cases based on the solution of a set of ordinary differential equations in a basis function format that are based on the electric field during the ECM process.

This method has a number of advantages. It allows for the use of geometric representations of the tool and workpiece, such as B-Splines and Bèzier curves. This enables easy integration with most current computer-aided design software. It is also possible more easily to design and simulate tools for non-ideal machining conditions, where parameters such as electrolyte conductivity vary with the ECM cell. Above all, this method can design tools directly for the ECM process, given a particular workpiece shape without iterative methods.

Computational trials have been carried out and compared with the results of an experimentally validated model. These showed that the method was effective for tool design under ideal machining conditions and was easier to use for non-ideal condition modelling.
Suppression of Bending Phenomenon of Steel Tube in Diameter Reduction by Cold Press
Authors: Okui T , Kuroda K , Akiyama M
Published: July 2006

A new die design is proposed for the suppression of the bending phenomenon that occurs in the cold-reduction process of the outside diameter of steel tube using a die. Numerical investigation by axi-symmetric elastic-plastic finite element analysis (FEA) was carried out in order to determine appropriate die geometry for the suppression of the bending phenomenon. The proposed die geometry suppresses the undershooting phenomenon by which the outside diameter of a worked tube is smaller than the inside diameter of the die, and ensures the contact of the tube outer surface to the bearing portion of the die to suppress the bending phenomenon. The key to the new die design for suppressing the undershooting phenomenon is the installation of a finishing zone with a small die angle where a small reduction of diameter is given to the tube. For suppressing the bending phenomenon, longer bearing length is necessary in addition to the suppression of undershooting. In order to examine the validity of the calculated result by FEA, a laboratory experiment was carried out on a steel tube with 0.45 per cent mass carbon content.
Kinematics and Workspace Analysis of a Six-Degree-of-Freedom Optic Fibre Positioning Stage Using the Denavit-Hartenberg Notation Method
Authors: Wang Fu-Shou , Chen Shang-Liang
Published: July 2006

This paper analyses a hybrid optic fibre alignment positioning stage with six degrees of freedom (6-DOF) based on a 3-DOF parallel kinematic mechanism and a 3-DOF serial mechanism. The parallel kinematic mechanism uses three different types of ball joint to provide rotation and sliding movement. The advantages of the parallel kinematic mechanism include a simple structure, simplified kinematic analysis, zero accumulation of link errors, and high positioning accuracy. This study commences by introducing the parallel kinematic mechanism of the positioning stage and then proceeds to discuss its degrees of freedom. The Denavit-Hartenberg notation method is employed to analyse the kinematics of the positioning stage. Some simulation results are given to verify the correctness of this study and to show some potential for the optical fibre alignment applications. In the sequel, the effects of the dimensions of the mechanical components of the positioning stage on the workspace are also investigated and discussed.
Processing of Collagen Gels to Create in Vitro Cell Growth Matrix Without Damage to the Collagen Native Structure
Authors: Liu Yang , Williams D J
Published: July 2006

This preliminary work explores a technique for processing collagen gels to provide a structured matrix support for cell growth and other tissue engineering applications without using cyto-toxic photo-initiators. Collagen gels can be structured by techniques similar to those of rapid manufacturing and retain the fibril structure of native collagen. Incorporation of alpha-modified minimal essential medium (MEM) in the collagen solution improved the rate of gelation in a cell-friendly way. Local gelation of a collagen solution formulated with alpha-modified MEM can be achieved by exposure to radiation from a remote incandescent lamp source indicating that it may be possible to prepare structured gels by lithographically based rapid manufacturing processes. Exposure of the alpha-modified MEM collagen solution to the radiation also increased the thickness of the collagen fibrils formed during the gelation process to create a more structured gel. Methyl blue staining, scanning electron microscope (SEM), and differential scanning calorimetry (DSC) experiments confirmed the collagen was not denatured, i.e. the native structure of collagen was retained.
Investigation of Cavitation Near the Orifice of Hydraulic Valves
Authors: Gao H , Lin W , Tsukiji T
Published: July 2006

Cavitating flows in the orifice of a poppet valve and a ball valve were investigated using an RNG k-ε turbulence model and a multi-phase flow cavitation model. The cavitation region, air volume fraction distribution, velocity distribution, and pressure distribution were obtained. Experimental flow visualization was conducted to catch cavitation images near the orifice of the poppet valve and the ball valve from two perpendicular directions, using a pair of industrial fibrescopes and high-speed video cameras-integrated visualization system. Besides, the vibrations of the valve body and the poppet induced by the cavitating flow are detected using a vortex displacement transducer, a laser displacement meter, and a digital strain device. The cavitation inception location and the cavitation cloud shape from both experiment and numerical simulations are in a good agreement qualitatively. Furthermore, the effects of outlet area, inlet velocity, and outlet pressure on cavitation were numerically investigated. The reduction of the outlet area by around 50 per cent is effective in reducing the cavitation near the orifice of the valve and suppressing the generation of cavitation. The cavitation region and the air volume fraction in the poppet valve increase greatly with an increased inlet velocity by 69 per cent on a certain condition. However, the increase in the outlet pressure can effectively suppress the cavitation inception in the poppet valve.
Model Identification of Linear Parameter Varying Aircraft Systems
Authors: Fujimori A , Ljung L
Published: July 2006

This article presents a parameter estimation of continuous-time polytopic models for a linear parameter varying (LPV) system. The prediction error method of linear time invariant (LTI) models is modified for polytopic models. The modified prediction error method is applied to an LPV aircraft system whose varying parameter is the flight velocity and model parameters are the stability and control derivatives (SCDs). In an identification simulation, the polytopic model is more suitable for expressing the behaviours of the LPV aircraft system than the LTI model from the viewpoints of the time and the frequency responses. The SCDs of the initial polytopic model are adjusted so as to fit the model output to the output data obtained from the LPV aircraft system.
Modified Stiffened Panel Analysis Methods for Laser Beam and Friction Stir Welded Aircraft Panels
Authors: Murphy A , Lynch F , Price M , Gibson A
Published: July 2006

The introduction of advanced welding methods as an alternative joining process to riveting in the manufacture of primary aircraft structure has the potential to realize reductions in both manufacturing costs and structural weight. Current design and analysis methods for aircraft panels have been developed and validated for riveted fabrication. For welded panels, considering the buckling collapse design philosophy of aircraft stiffened panels, strength prediction methods considering welding process effects for both local-buckling and post-buckling behaviours must be developed and validated. This article reports on the work undertaken to develop analysis methods for the crippling failure of stiffened panels fabricated using laser beam and friction stir welding. The work assesses modifications to conventional analysis methods and finite-element analysis methods for strength prediction. The analysis work is validated experimentally with welded single stiffener crippling specimens. The experimental programme has demonstrated the potential static strength of laser beam and friction stir welded sheet-stiffener joints for post-buckling panel applications. The work undertaken has demonstrated that the crippling behaviour of welded stiffened panels may be analysed considering standard-buckling behaviour. However, stiffened panel buckling analysis procedures must be altered to account for the weld joint geometry and process altered material properties.
Optimal Sliding Mode Manoeuvring Control and Active Vibration Reduction of Flexible Spacecraft
Authors: Hu Q , Ma G
Published: July 2006

A hybrid control scheme for vibration of flexible spacecraft during manoeuvring operations is proposed in this paper. The new scheme integrates the method of optimal sliding mode control (OSMC) and the technique of active vibration suppression. In this control strategy, the technique of active vibration control using smart materials is first used actively to suppress certain flexible modes by designing optimal positive position feedback (OPPF) compensators that add damping to the flexible structures in certain critical modes in the inner feedback loop. For the outer loop, the OSMC theory is used to slew the spacecraft by minimizing the expected value of a quadratic objective function consisting of only desired errors with the constraints that desired error states always remain on the intersection of sliding surfaces. The advantage in this scheme is that the vibration reduction and attitude control are achieved separately in the two separate feedback loops, allowing the pointing requirements and simultaneous vibration suppression to be satisfied independent of one another. To study the effectiveness of the corresponding hybrid control scheme, initially a collocated proportional plus derivative (PD) control is developed to control the rigid body motion. The performances of the controllers are assessed in terms of the attitude pointing accuracy and vibration reduction as compared to the response with PD control and the PD-based hybrid control. Moreover, linear-quadratic Gaussian (LQG) control has also been developed to design the attenuator, and in view of vibration suppression the performance of LQG compensator is also compared with the response with the OPPF control. Both analytical and numerical results are presented to show the theoretical and practical merits of this approach.
Photoelectric Behavior of Sublimed Films of Phenothiazine Derivatives
Authors: Yoshida Sadamu , Kozawa Kozo , Sato Naoki , Uchida Tokiko
Published: July 2006

The energy structures and photoelectric behavior of sandwich-type organic photocells, configurations of which are Au/benzo[b]phenothiazine/Al, Al/dibenzo[a,h]phenothiazine/In, Al/dibenzo[a,j]phenothiazine/In, and Au/triphenodithiazine/Al, are investigated. The electrical and photovoltaic measurements show that the blocking contacts are formed at the pigments/Al interfaces in these four cells. These experimental results are consistent with the proposed energy band structures of the cells, which are estimated on the basis of the experimental results of ultraviolet photoelectron spectra and the threshold values in photocurrent action spectra.