bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of a Nephelometric Procedure for the Determination of Alpha‐fetoprotein in Amniotic Fluid
Authors: FITZGERALD D. , SIMON F.
Published: February 2009

Previous work (Brock, Lancet, 2, 197, 1972) has established that Alpha‐fetoprotein (AFP) is elevated in amniotic fluid from open neuro‐tubular defective pregnancies. This report describes a simple quantitative immunonephelometric method for measurement of AFP in amniotic fluid.

Immunonephelometry measures the amount of light scattered by soluble antigen‐antibody complexes. Complex formation is proportional to the antigen concentration, resulting in a proportional increase in light scattered. A modified Kallestad nephelometer was used for this study. It consists of a tungsten light source with a filter at 610 nm and two photodetector cells at 90° with respect to light source.

The assay procedure requires mixing a 100 μl sample of amniotic fluid with 2 ml of goat anti‐AFP (dilution 1:50) in 4% PEG‐saline. The assay requires a 60 minute incubation at room temperature. The standard curve covers the range 773 to 21,775 I.U./ml, with a minimum detectable dose of 120 I.U./ml. Precision is good, with an interassay coefficient of variation of < 4% using low, medium, and high controls. Recovery of AFP added varied from 92 to 100%. The method correlates well with radioimmunoassay (r = 0.97, n = 37) and the slope is not significantly different from one (p<0.001).

In summary, our nephelometric procedure is rapid, reproducible and sensitive, offering advantages over currently employed methods.
Alpha‐fetoprotein: Is the Pattern of Concanavalin A‐affinity Molecular Variants a Marker for Synthesis by Neoplastic Cells in the Rat?
Authors: KELLEHER P. C. , McMAHON J. B. , BARUS M. , SMITH C. J.
Published: February 2009

The post‐secretory metabolism of the two concanavalin A‐affinity molecular variants of rat alpha‐fetoprotein was studied in normal adult rats. The serum half‐lives of the two alpha‐fetoprotein molecular variants and unfractionated alpha‐fetoprotein are the same. There is no quantitatively significant interconversion of the two alpha‐fetoprotein concanavalin A‐affinity molecular variants in normal adult rat serum. These results indicate that the pattern of alpha‐fetoprotein concanavalin A‐affinity molecular variants present in rat serum reflects their relative rates of synthesis rather than differences in their rates of catabolism following secretion from the liver cell.
Morphological Difference Between Non‐AFP‐producing and AFP‐producing Hepatocellular Carcinomas (HC)
Authors: HANAK H. , EDER G. , WEISS W.
Published: February 2009

Eight non‐AFP‐producing HC are compared with unselected AFP‐producing ones. All patients were males and suffered from cirrhosis. As criteria for biological malignancy only invasion of blood vessels and/or metastases were accepted. The patients' sera were tested during life at least twice by means of a modified electrophoretic method and the RIA. The comparison of both groups with regard to growing type, grade of differentiation, production of bile, metastasizing, necrosis, and duration of subjective symptoms before death seems to indicate a somewhat more ‘benign’ behaviour of non‐AFP‐producing HC.
Postoperative Differentiation of Local Tumor Recurrence and Generalized Metastasizing in Patients with Adenocarcinomas of the Digestive System by CEA Follow‐up Study
Authors: STAAB H. J. , ANDERER F. A. , STUMPF E. , FISCHER R.
Published: February 2009

371 patients with histologically confirmed adenocarcinomas of the digestive system were postoperatively monitored by analysis of the time course of the CEA concentration in the serum. The tendencies of the time courses of the computerized CEA surveillance diagrams allowed an early prognosis of local tumor recurrence or of generalized metastasizing. The diagnosis of a relapse on the basis of a rise in CEA concentration preceded a positive clinical diagnosis up to 10 months. The diagnosis was confirmed by second‐look operation or by other diagnostic means. The analysis of the CEA time courses made it possible to differentiate local tumor recurrence and generalized metastasizing.
Nonspecific Crossreacting Antigen (NCA) in Human Mammary Carcinoma Extracts
Authors: NIELSEN C. SCHÄAFER , WANDALL J. H.
Published: February 2009

Human mammary carcinoma (HMC) homogenates from 28 patients and mammary hyperplasia (MH) homogenates from 20 patients undergoing reduction mammoplasty were used as antigens in preparing antibodies in rabbits. Crossed immunoelectrophoresis of HMC extracts against the corresponding antibodies revealed one major precipitate not present in MH. This antigen was present in separately prepared extracts of breast tissue from 3 out of 10 patients with HMC. Antibody titre was unchanged following absorption with MH, normal human liver, kidney, skin and serum. Immunochemical crossreaction with pregnancy zone proteins, alpha‐1‐fetoprotein, ferritin, lactoferrin, plasma, extracts of human placenta and fetal and adult liver did not occur. The antigen could not be demonstrated by rocket immunoelectrophoresis of sera from patients with HMC. Small amounts of the antigen were found in extracts from human spleen and renal carcinoma and larger amounts in extracts from human peripheral granulocytes, but not in preparations of mononuclear leucocytes (98% pure). Tandem crossed immunoelectrophoresis of extracts from HMC and carcino embryonic antigen against antibodies prepared against HMC revealed a reaction of partial identity between the two antigens, and antisera prepared against carcino embryonic antigen contained precipitating antibodies against the HMC antigen. The HMC antigen was eventually identified as nonspecific crossreacting antigen (NCA) described by other authors.
New Applications of Carcinoembryonic Antigen and Alpha‐fetoprotein Assays in Clinical Diagnosis
Authors: BREBOROWICZ D. , MAJEWSKI P. , MADEJA Z. , BREBOROWICZ J.
Published: February 2009

The radioimmunoassay measurements of CEA and AFP together with cytological examination were performed in 63 samples of pleural or peritoneal exudates obtained from patients with different malignancies. Elevated levels of CEA and/or of AFP were detected in 22 of 29 cytologically positive samples, in 3 of 6 cytologically suspected samples and in 24 of 28 cytologically negative samples. In 30 patients with abdominal tumours the concentrations of CEA and AFP were compared in peripheral circulation and in the veins draining tumours. In 16 of these patients concentration of either CEA or AFP was higher than in the peripheral circulation. The value of measurements of CEA and AFP in exudates and in blood from veins draining tumours for differential diagnosis is discussed.
Novel Gamma‐glutamyl Transpeptidase Isoenzyme Occurring in Sera of Patients with Hepatoma
Authors: HATTORI N. , SAWABU N. , NAKAGEN M. , ISHII M.
Published: February 2009

In view of carcinoembryonic properties with respect to γ‐GTP, we investigated whether or not hepatoma specific γ‐GTP isoenzyme was found in the sera of patients with hepatoma. Fractionations of serum γ‐GTP were carried out in sera from 229 patients with various hepatobiliary diseases including 68 with hepatoma by polyacrylamide gradient gel electrophoresis. The band II which was seen in the region near to ceruloplasmin could be detected in 25 out of the 68 patients with hepatoma (37%), but not in the patients with other diseases. In addition to the II band, an extra band (II) was found in 15 of these 25 patients. The band II and II′ could not be found in any groups of patients studied except hepatoma patients. It was presumed that band II and II′ could be specific for hepatoma.
Determination of Placental Alkaline Phosphatase‐Regan Isoenzyme in Cancer Sera by a Sensitive Radioimmunoassay
Authors: HOLMGREN P.‐A. , STIGBRAND T. , DAMBER M. , VON SCHOULTZ B. , WAHREN B.
Published: February 2009

Three common genetically classified placental alkaline phosphatase variants (F, I, S) were purified to complete homogeneity. Specific antisera were raised against all three types. Complete fusion reactions in double diffusion tests were obtained for all combinations of antigen and antibody, indicating close immunological relatedness.

A sensitive and specific double antibody solid phase (DASP) radioimmunoassay with a least detectable dose of 9 ng/ml was developed.

Sera from 241 patients with different malignant disorders were assayed for the presence of placental alkaline phosphatase, also called the Regan isoenzyme. Significantly elevated values were obtained in only one case of embryonal carcinoma. This corresponds to a frequency of 0.4%. Three selected sera from cancer patients with a known content of Regan isoenzyme were tested in the same assay and had elevated values.
Modulation Studies of Alkaline Phosphatase in Human Choriocarcinoma Cells
Authors: SPEEG K. V. , AZIZKHAN J. C. , STROMBERG K.
Published: February 2009

The BeWo line of human choriocarcinoma has been studied in an attempt to understand the phased expression of AP in normal placenta and genome derepression in certain cancers. Be Wo contains at least two species of AP. The major activity is heat‐stable and has amino acid inhibition characteristics similar to the D‐variant isoenzyme of normal term placenta. The other activity is heat‐labile and has characteristics which suggest it may be the same as the AP isoenzyme recently found in first trimester placenta. In Be Wo, AP is not influenced by cAMP. Both AP activities can be increased by butyrate. Halogenated pyrimidines are known to increase AP activity in cell lines with low constitutive activity. In BeWo, IdU results in increased activity of both heat‐stable AP and heat‐labile AP. The time course of increased activity as well as the ability to prevent the increase with excess TdR suggest that IdU must be incorporated into DNA to have an effect.
Gamma‐glutamyl Transferase as Oncofetal Marker of Experimental Hepatocarcinogenesis in the Rat
Authors: KALENGAYI M. M. R. , DESMET V. J.
Published: February 2009

γ‐Glutamyl transferase (γ‐GTase) is abundant in the fetal and neonatal rat liver, but almost completely disappears in the normal adult rat liver. Aflatoxin B1 (AFB1) was used in several hepatocarcinogenic models in the rat. The hepatocarcinogenesis was divided in early, preneoplastic and neoplastic phases during which liver histological changes were studied in correlation with histochemical analysis of γ‐GTase.

Five types of hepatocyte populations were encountered: original hepatocytes, small newly formed hepatocytes and transitional cells, early liver cell regenerative areas, late liver cell foci and nodules and evidently malignant liver cells. A very marked γ‐GTase activity always resurged reversibly in every area of proliferating newly formed hepatocytes and transitional cells and in every early regenerative area, but it reappeared irreversibly in every late appearing focus and nodule and in every hepatocellular carcinoma. The whole remaining parenchyma (original hepatocytes) showed no γ‐GTase activity, as in the normal adult rat liver. The resurgence of γ‐GTase in these subsequent cell populations, including the malignant hepatocytes, emphasizes that the development of the latter implicates the reacquiring of some embryonal biochemical characteristics. Furthermore it illustrates the similar immature state of specific and focal preneoplastic and neoplastic liver cell lesions. γ‐GTase histochemically proved to be the most sensitive marker of the hepatocarcinogenic process.
Isozyme Ratios of Human Serum 5‘‐Nucleotide Phosphodiesterase
Authors: TSOU K. C. , LO K. W.
Published: February 2009

The presence of five isozymes of 5′‐nucleotide phosphodiesterase in human sera and the use of the fast‐moving isozyme‐V as a diagnostic aid for human primary and secondary hepatoma (liver metastasis) have been reported from our laboratories. The present paper describes further work in the use of isozyme ratio for the possible discrimination of the two groups of patients.

Tissue enzyme study has defined both IV and V as from liver, and III from colon. The ratios for V/IV and (IV + V)/III were therefore possibly significant for this purpose. Our sampling indicates that for primary hepatoma V/IV = 0.78±0.56 and for liver metastasis V/IV = 0.96±0.57 (p>0.05). On the other hand (V + IV)/III = 0.76 ±0.52 for primary hepatoma, and (V + IV)/III = 1.12±0.64 for secondary hepatoma (p == 0.05). It is therefore possible to improve the discrimination of secondary hepatoma from primary hepatoma with the aid of isozyme ratio study. Clusters in scatterogram for these groups are discussed.
Pregnancy Specific β1‐glycoprotein: Reference Values and Physiological Variations in Normal Pregnancy
Authors: SCHULTZ‐LARSEN P.
Published: February 2009

A 90% general reference area of the pregnancy specific β1‐glycoprotein (SP‐1 or PSβG) is estimated on the basis of 387 samples from normal pregnancies. This is carried out by means of a rocket‐immunoelectrophoresis. In the second and third trimester the SP‐I concentration shows a skew distribution for which reason non‐parametric statistical methods are used. After birth of the placenta the half‐life of SP‐1 in serum is found to be of 34–60 hours. The day to day variations are found to be of 1.1%‐3.2% and the diurnal variations: 2.3% 6.4%. Serial determinations in 41 normal pregnancies show very limited divergencies from the average curve.

SP‐1 concentration in the 37th week shows a negative correlation to maternal age, and positive correlations to placental weight and hPL in serum but not to the urinary excretion of estriol.

It is concluded that to a reasonable degree the SP‐1 concentration in serum fulfil the criteria of a placental‐function variable. Because of the broad general reference area and the small divergencies in the individual course. serial determinations are expected to give more precise information than single determinations.
Pregnancy Specific β1‐glycoprotein in Threatened Abortion
Authors: SCHULTZ‐LARSEN P. , HERTZ J.
Published: February 2009

The aim of this study was to elucidate the prognostic value of the pregnancy specific β1‐glycoprotein (SP‐I == PS/βG) of maternal serum in threatened abortion.

Determinations were made by rocket‐immunoelectrophoresis with a detection limit of I mg/1.

59 patients with vaginal bleeding and positive pregnancy tests entered the final material. 33 gave birth after the 28th week, 26 had a spontaneous abortion.

Serum samples were taken until birth or spontaneous abortion.

After the 9th gestational week a separation of the serum concentrations was observed between the patients who had a spontaneous abortion and those who gave birth. It is concluded that the SP‐1 determination might be of great prognostic value in threatened abortion.
The Immunohistochemical Detection of Chorionic Gonadotropin in Experimental Rat Hepatomas
Authors: MALKIN A. , KELLEN J. A. , KOLIN A. , CAMERON R. , FARBER E.
Published: February 2009

Using a peroxidase labelled antibody technique, the presence of chorionic gonadotropin or a substance closely related antigenically has been demonstrated in putative preneoplastic hepatocytes in the rat during carcinogenesis induced by diethylnitrosamine (DEN) as well as in hepatomas induced by DEN or by 2‐acetylaminofluorene (2‐AAF), a solid hepatoma derived from HTC cells and in the 5123 Morris hepatoma and two of its variants. Chorionic gonadotropin is a normal product of the syncytiotrophoblast. Consequently, its detection in an experimental hepatoma as well as in putative preneoplastic cells may represent a unique manifestation of the appearance in these experimental tumor models of gestational elements which may play a role as components of a programmed phenomenon early in the carcinogenic process.
An Oncofetal Haptoglobin: A Fetal Haemoglobin Binding Protein in Malignancy
Authors: RAAM S. , COHEN J. L.
Published: February 2009

We have previously described a protein in human neonatal cord sera having functional characteristics of adult haptoglobin. This protein has electrophoretic and immunological properties which distinguish it from adult serum haptoglobins, 2 1. 2–2 and 1–1.

In this report we discuss the characteristics of this ‘fetal protein’ isolated from a malignant pleural fluid of a patient with lung cancer. Data are presented to indicate the identity of this protein to the fetal haemoglobin binding protein of human neonatal cord sera.
Clinical Significance of Leukemia Associated Antigen (LAA) in Human Serum
Authors: NOER G. , BERG K. , STAVEM P.
Published: February 2009

Antiserum to serum leukemia associated antigen (LAA) was produced by immunizing rabbits or sheep with leukemic blast cells or fetal cells. This, as well as its presence in amniotic fluid and fetal tissue identifies LAA as another oncofetal component. LAA was present in the serum of 1% of healthy blood donors. In a longitudinal study of leukemia patients, LAA was found, at one stage or the other, in 50–75% of patients with acute leukemia or chronic myelogenous leukemia, but only in 27% of persons with chronic lymphocytic leukemia. A difference between those who obtained and those who did not obtain a remission was observed, since significantly more patients in the latter group had LAA at the initial test. Among these who obtained a remission, appearance of LAA seemed to signal a turn for the worse. These findings with qualitative tests were confirmed by the quantitative ‘rocket’ technique. The exact nature of LAA is the subject of present studies.
Immunochemical Biological Markers and Hereditary Cancer Risk
Authors: GUIRGIS H. A. , LYNCH H. T. , HARRIS R. E. , VANDEVOORDE J. P.
Published: February 2009

The utilization of multiple biological markers in cancer may embellish the predictive value of any single marker. We have studied several putative biological markers of cancer risk (CEA, AFP, AHH, %T, %B lymphocytes, and immunoglobulins, IgA, IgM, IgG) in relatives at high genetic risk for cancer within a kindred manifesting the cancer family syndrome. Thirteen of the 19 individuals sampled were themselves unaffected progeny of affected direct genetic line parents. The remaining six individuals studied manifested cancer. In this report, we describe a method of derivation of an index utilizing results from five of the seven putative biological markers tested and the index scores were then obtained for each individual. The number of individuals manifesting a significant index score was compared with the number expected to carry the deleterious gene among the 13 unaffected progeny of affected parents. The observed number of aberrant index scores agrees precisely with that expected based upon gene segregation and the age distribution of the sample. The proposed index appears to provide predictability of cancer risk status in accord with mathematical expectations for a simple genetic model.
Prevalence and outcome of fungal infection in patients with severe acute pancreatitis
Authors: Kochhar Rakesh , Ahammed S K Mahiuddin , Chakrabarti Arunaloke , Ray Pallab , Sinha Saroj K , Dutta Usha , Wig Jai Dev , Singh Kartar
Published: February 2009

Background and Aim:  To study the prevalence of risk factors and outcome of fungal infections in patients with severe acute pancreatitis.

Methods:  Fifty consecutive patients with severe acute pancreatitis were investigated for evidence of fungal infection by weekly culture of body fluids and aspirate from pancreatic/peripancreatic tissue and samples collected at necrosectomy. All patients were managed as per a standard protocol. Patients with documented fungal infection were treated with intravenous amphotericin or fluconazole. Data were analyzed using SPSS software (version 13), and risk factors for fungal infection and mortality were determined.

Results:  Fungal infection was documented in 18 (36%) of 50 patients with Candida albicans (the commonest species). The incidence of fungal infection steadily increased with increasing duration of hospital stay. Those with fungal infection more often had evidence of respiratory failure (P = 0.031) and hypotension (P = 0.031) at admission, prolonged hospital stay > 4 weeks (P = 0.034), longer duration of antibiotics (P = 0.003), received total parenteral nutrition (P = 0.005), and required mechanical ventilation (P = 0.001) in contrast to those without fungal infection. The logistic regression analysis found the independent risk factors for fungal infection to be antibiotic therapy for > 4 weeks and hypotension at hospitalization. Of the 18 patients with fungal infection, 13 were administered intravenous antifungals; eight of these patients survived, while the five who did not receive antifungals died.

Conclusion:  Fungal infection was detected in 36% of our patients. The independent risk factors associated with it were hypotension at hospitalization and prolonged antibiotic therapy. Antifungal therapy improved their chances of survival.
Isoflavones regulate innate immunity and inhibit experimental colitis
Authors: Morimoto Masakazu , Watanabe Tomohiro , Yamori Masashi , Takebe Minoru , Wakatsuki Yoshio
Published: February 2009

Background and Aim:  Dysregulated immune responses in the gut to luminal antigens can cause inflammatory bowel diseases (IBD). The roles played by dietary antigens in the pathogenesis or prevention of IBD are poorly understood. Soybean isoflavones are digested in large amounts and have many biological activities. The aim of this study was to determine whether isoflavones in aglycon and bioavailable forms have any effect on gut immunity and protect the host from tissue damage in a mouse model of colitis.

Methods:  We administered daidzein‐rich isoflavone aglycones (DRIA) to mice for 1 week and then treated them with 2% dextran sodium sulfate (DSS) in drinking water for 4 days to induce colitis. The effect of DRIA was evaluated by examining the histopathology of the colon, body weight changes, and functional analysis of mesenteric lymph node cells (MLN).

Results:  DRIA inhibited interleukin (IL)‐6 and IL‐8 production by Toll‐like receptor (TLR)2, and TLR4‐stimulated monocytes in a dose‐dependent manner. The mice administered DRIA had less inflammation and tissue damage in the colon than the control mice. This protective effect of DRIA was associated with a decrease in interferon‐γ, IL‐6, and IL‐12p40 secretion, and an increase in IL‐10secretion and low cell‐activation status of antigen‐presenting cells (APC) in MLN.

Conclusion:  Ingested DRIA can downregulate the functions of APC and inhibit DSS colitis.
Na+/H+ exchanger mediates TNF‐α‐induced hepatocyte apoptosis via the calpain‐dependent degradation of Bcl‐xL
Authors: Liu Zhan , Wang Shuangxi , Zhou Huixin , Yang Yuming , Zhang Mingliang
Published: February 2009

Background and Aim:  It is well known that tumor necrosis factor‐α (TNF‐α) induces hepatocyte apoptosis and contributes to liver diseases. However, the exact mechanisms are not well understood.

Methods:  In the present study, we reported that Na+/H+ exchanger (NHE) is involved in TNF‐α‐induced hepatocyte apoptosis.

Results:  TNF‐α time dependently induced an increase in NHE activity in hepatocytes, but cariporide, an NHE inhibitor, blocked the TNF‐α‐induced increase of NHE activity in a dose‐dependent manner. Increased NHE activity induced by TNF‐α was associated with increased intracellular calcium (Ca2+i) concentration and calpain activity. Cariporide reversed these effects induced by TNF‐α. In addition, TNF‐α downregulated Bcl‐xL, an anti‐apoptotic protein, but not mRNA levels. The inhibition of either calpain or NHE blocked the TNF‐α‐induced decrease of the Bcl‐xL protein. TNF‐α did not change the pro‐apoptotic Bax and Bak protein levels. Cariporide, calcium remover 1,2‐bis (2‐aminophenoxy) ethane‐N,N,N0,N0–tetraacetic acid, or calpain inhibitor benzyloxycarbonyl‐leucyl‐leucinal attenuated TNF‐α‐induced hepatocyte apoptosis.

Conclusion:  TNF‐α via NHE results in hepatocyte apoptosis through the calcium/calpain/Bcl‐xL pathway.
Effects of probucol on hepatic tumor necrosis factor‐α, interleukin‐6 and adiponectin receptor‐2 expression in diabetic rats
Authors: Zhang Xia , Li Zhongzhuan , Liu Dongfang , Xu Xin , Shen Wei , Mei Zhechuan
Published: February 2009

Background and Aims:  Probucol is a lipid‐lowering agent with anti‐oxidant effects. Oxidative stress and inflammation are important in the pathophysiology of insulin resistance. We aimed to evaluate the effects of probucol on liver histological changes, serum and hepatic levels of adipokines in rats with high fat‐induced type 2 diabetes (T2D).

Methods:  Thirty‐six rats were divided into a normal control group, a high fat‐induced T2D group and a probucol treatment group. After six weeks of treatment with probucol, we evaluated liver histological changes and measured homeostasis model assessment index (HOMA‐IR), serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, adiponectin and hepatic TNF‐α, IL‐6 and adiponectin receptor‐2 (adipoR2) mRNA.

Results:  The degree of hepatic steatosis and inflammation, HOMA‐IR, serum ALT, TNF‐α and IL‐6 concentrations, and hepatic TNF‐α and IL‐6 mRNA expression in diabetic rats were significantly higher compared with normal controls. Serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression in diabetic rats were significantly lower compared with normal controls. Probucol significantly reduced the degree of hepatic steatosis, HOMA‐IR, serum ALT, TNF‐α and IL‐6 concentrations, and hepatic TNF‐α and IL‐6 mRNA expression. Probucol significantly raised serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression.

Conclusions:  In rats with high fat‐induced T2D, treatment with probucol improved insulin sensitivity, hepatic steatosis by raising circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro‐inflammatory cytokines in the circulation and liver.
Echographic detection of diethylnitrosamine‐induced liver tumors in rats and the effect of the intratumoral injection of an inhibitor of c‐Jun N‐terminal kinase
Authors: Hanajiri Kazuyuki , Mitsui Hiroshi , Maruyama Toshiyuki , Hashimoto Naoaki , Sata Masataka , Omata Masao
Published: February 2009

Background and Aim:  There have so far been few reports describing echographic studies of chemically‐induced carcinogenesis in rodent livers. Using echography, we observed diethylnitrosamine‐induced liver tumors in rats and examined the effect of an intratumoral injection of an inhibitor of c‐Jun N‐terminal kinase.

Methods:  Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c‐Jun N‐terminal kinase, on the growth of rat hepatoma cell line McA‐RH7777 was tested in vitro. Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.

Results:  The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA‐RH7777 cells. After SP600125 was injected in vivo, the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.

Conclusions:  Our results indicate that echography is quite useful for follow‐up studies of liver carcinogenesis in rats, and c‐Jun N‐terminal kinase might be another therapeutic target in liver neoplasms.
Laser capture microscopy in a study of expression of structural proteins in the cuticle cells of human hair
Authors: Rogers George , Koike Kenzo
Published: February 2009

Abstract:  The cuticle of human hair consists of several layers of flat cells that are hardened through their content of cross‐linked proteins and protect the hair structure from the environment. Known proteins in the cuticle are the sulphur‐rich KAP 5 and KAP10 proteins located in the exocuticle and cross‐linked by disulphide bonds. Isopeptide bonds are also present and led to a proposal from amino acid analysis that the surface of cuticle cells also contains keratinocyte cell envelope proteins, loricrin, involucrin and small proline‐rich proteins that contribute to the stability of the hair cuticle. Confirmation of that proposal by protein chemical methods is difficult because of the insolubility of the surface membranes. In the previous studies by other authors, involucrin was not detected in the cuticle by in situ hybridization or by immunoelectron microscopy with specific antibodies. An alternative approach was undertaken to determine whether mRNAs encoding keratinocyte envelope proteins are expressed in cuticle cells in the human hair follicle. The study utilized dissection of the cuticle, cortex and inner root sheath layers from follicles by laser capture microscopy. RNA was isolated and subjected to PCR analysis with specific primers to detect expression of mRNAs encoding cell envelope proteins. Their presence in the cuticle was not detected, and it was concluded that the proteins they encode are not produced. The structural consequences including the possibility that KAPs 5 and 10 are the prime components cross‐linked by both disulphide and isopeptide bonds are discussed.
Kinematic Kalman Filter (KKF) for Robot End-Effector Sensing
Authors: Jeon Soo , Tomizuka Masayoshi , Katou Tetsuaki
Published: February 2009

In control of industrial manipulators, the position from the motor encoder has been the only sensor measurement for axis control. In this case, it is not easy to estimate the end-effector motion accurately because of the kinematic errors of links, joint flexibility of gear mechanisms, and so on. Direct measurement of the end-effector using the vision sensor is considered as a solution but its performance is often limited by the slow sampling rate and the latency. To overcome these limitations, this paper extends the basic idea of the kinematic Kalman filter (KKF) to general rigid body motion leading to the formulation of the multidimensional kinematic kalman filter (MD-KKF). By combining the measurements from the vision sensor, the accelerometers and the gyroscopes, the MD-KKF can recover the intersample values and compensate for the measurement delay of the vision sensor providing the state information of the end-effector fast and accurately. The performance of the MD-KKF is verified experimentally using a planar two-link robot. The MD-KKF will be useful for widespread applications such as the high speed visual servo and the high-performance trajectory learning for robot manipulators, as well as the control strategies which require accurate velocity information.
Online Switching Control of LFT Parameter-Dependent Systems
Authors: Dong Ke , Wu Fen
Published: February 2009

To improve controlled performance and expand gain-scheduling control capability, we propose a switching control approach of linear fractional transformation parameter-dependent systems using multiple Lyapunov functions combined with online control techniques. At each switching instant, a gain-scheduled controller working for the next switching interval will be designed online. The switching control synthesis condition is formulated as linear matrix inequalities and can be solved efficiently, upon which the controller will be constructed. The online switching control scheme is demonstrated using an uninhabited combat aerospace vehicle problem.
Transient Simulation of the Aerodynamic Response of a Double-Deck Bus in Gusty Winds
Authors: Hemida Hassan , Krajnović Siniša
Published: February 2009

The purpose of the research reported in this paper was to investigate the aerodynamic response of a double-deck bus in gusty winds using a detached-eddy simulation (DES). The bus was subjected to three different scenarios of wind gusts: gust in a wind tunnel, gust in a natural wind, and gust behind the exit of a tunnel. The proposed scenarios of gusts are in the time domain and take into account the dynamic behavior of natural winds. The Reynolds number of the flow, based on the time-averaged speed of the side wind and a reference length of 0.1 m, was 1.3×106. Detailed transient responses of the aerodynamic coefficients and flow structures were investigated. Good agreement was found between the DES results and the available experimental data. A comparison between the influence of the different gust scenarios on the aerodynamic coefficients shows that the gust behind the exit from a tunnel has a stronger influence on the aerodynamics than the other gust scenarios. Moreover, the influence of the gusts on the time history of aerodynamic coefficients is found to be limited to the period of the gust.
Assessment Measures for Engineering LES Applications
Authors: Celik I. , Klein M. , Janicka J.
Published: February 2009

Anticipating that large eddy simulations will increasingly become the future engineering tool for research, development, and design, it is deemed necessary to formulate some quality assessment measures that can be used to judge the resolution of turbulent scales and the accuracy of predictions. In this context some new and refined measures are proposed and compared with those already published by the authors in the common literature. These measures involve (a) fraction of the total turbulent kinetic energy, (b) relative grid size with respect to Kolmogorov or Taylor scales, and (c) relative effective subgrid/numerical viscosity with respect to molecular viscosity. In addition, an attempt is made to segregate the contributions from numerical and modeling errors. Proposed measures are applied to various test cases and validated against fully resolved large eddy simulation and/or direct numerical simulation whenever possible.
Swimming and Flying in Nature—The Route Toward Applications: The Freeman Scholar Lecture
Authors: Bandyopadhyay Promode R.
Published: February 2009

Evolution is a slow but sure process of perfecting design to give a life-form a natural advantage in a competitive environment. The resulting complexity and performance are so sophisticated that, by and large, they are yet to be matched by man-made devices. They offer a vast array of design inspirations. The lessons from swimming and flying animals that are useful to fluids engineering devices are considered. The science and engineering of this subject—termed “biorobotics” here—are reviewed. The subject, being of dynamic objects, spans fluid dynamics, materials, and control, as well as their integration. The emphasis is on understanding the underlying science and design principles and applying them to transition to human usefulness rather than to conduct any biomimicry. First, the gaps between nature and man-made devices in terms of fluids engineering characteristics are quantitatively defined. To bridge these gaps, we then identify the underlying science principles in the production of unsteady high-lift that nature is boldly using, but that engineers have preferred to refrain from or have not conceived of. This review is primarily concerned with the leading-edge vortex phenomenon that is mainly responsible for unsteady high-lift. Next, design laws are determined. Several applications are discussed and the status of the closure of the gaps between nature and engineering is reviewed. Finally, recommendations for future research in unsteady fluids engineering are given.
Networked Assembly of Mechatronic Linear Physical System Models
Authors: Radcliffe Clark J. , Motato Eliot , Reichenbach Drew
Published: February 2009

Engineering design is evolving into a global activity. Globally distributed design requires efficient global distribution of models of dynamic physical systems through computer networks. These models must describe the external input-output behavior of the electrical, mechanical, fluid, and thermal dynamics of engineering systems. An efficient system model assembly method is then required to assemble these component system models into a model of a yet higher-level dynamic system. Done recursively, these higher-level system models become possible components for yet higher-level analytical models composed of external model equations in the same standardized format as that of the lowest level components. Real-time, automated exchange, and assembly of engineering dynamic models over a global network requires four characteristics. The models exchanged must have a unique standard format so that they can be exchanged and assembled by an automated process. The exchange of model information must be executed in a single-query transmission to minimize network load. The models must describe only external behavior to protect internal model details. Finally, the assembly process must be recursive so that the transfer and assembly processes do not change with the level of the model exchanged or assembled. This paper will introduce the modular modeling method (MMM), a modeling strategy that satisfies these requirements. The MMM distributes and assembles linear dynamic physical system models with a dynamic matrix representation. Using the MMM method, dynamic models of complex assemblies can be built and distributed while hiding the topology and characteristics of their dynamic subassemblies.
Measurement-Level Integration of Carrier-Phase GPS and Laser-Scanner for Outdoor Ground Vehicle Navigation
Authors: Joerger Mathieu , Pervan Boris
Published: February 2009

This paper introduces a navigation system based on combined global positioning system (GPS) and laser-scanner measurements for outdoor ground vehicles. Using carrier-phase differential GPS, centimeter-level positioning is achievable when cycle ambiguities are resolved. However, GPS signals are easily attenuated or blocked, so their use is generally restricted to open-sky areas. In response, in this work we augment GPS with two-dimensional laser-scanner measurements. The latter is available when GPS is not and further enables obstacle detection. The two sensors are integrated in the range domain for optimal navigation performance. Nonlinear laser observations and time-correlated code and carrier-phase GPS signals are processed in a unified and compact measurement-differencing extended Kalman filter. The resulting algorithm performs real-time carrier-phase cycle ambiguity estimation and provides absolute vehicle positioning throughout GPS outages, without a priori knowledge of the surrounding landmark locations. Covariance analysis, Monte Carlo simulations, and experimental testing in the streets of Chicago demonstrate that the performance of the range-domain integrated system far exceeds that of a simpler position-domain implementation, in that it not only achieves meter-level precision over extended GPS-obstructed areas, but also improves the robustness of laser-based simultaneous localization and mapping.
On Stability Problems of Supply Networks Constrained With Transport Delay
Authors: Sipahi Rifat , Lämmer Stefan , Helbing Dirk , Niculescu Silviu-Iulian
Published: February 2009

Transportation is one of the most crucial components in supply networks. In transportation lines, there exists a finite time between products leaving a point and arriving to another point in the supply network. This period of time is the delay, which accompanies all transportation lines present in the entire network. Delay is a well-known limitation, which is inevitable and pervasive in the network causing synchronization problems, fluctuating or excessive inventories, and lack of robustness of inventories against cyclic perturbations. The end results of such undesirable effects directly reflect to costs. This paper is motivated to reveal the mechanisms leading to these problems by analytically characterizing qualitative behavior of supply network dynamics modeled by continuous-time differential equations. The presence of delay forms the main challenge in the analysis and this is tackled by developing/utilizing the tools emerging from delay systems and control theory. While the backbone of the paper addresses the qualitative behavior in presence of a single delay representing delays in all transportation paths, it also reveals how to choose production rates and transportation delay without inducing any undesirable effects mentioned. Thorough cases studies with single and multiple delays are presented to demonstrate the effectiveness of the approaches proposed.
Testing and Modeling of MR Damper and Its Application to SDOF Systems Using Integral Backstepping Technique
Authors: Ali Sk. Faruque , Ramaswamy Ananth
Published: February 2009

Magnetorheological dampers are intrinsically nonlinear devices, which make the modeling and design of a suitable control algorithm an interesting and challenging task. To evaluate the potential of magnetorheological (MR) dampers in control applications and to take full advantages of its unique features, a mathematical model to accurately reproduce its dynamic behavior has to be developed and then a proper control strategy has to be taken that is implementable and can fully utilize their capabilities as a semi-active control device. The present paper focuses on both the aspects. First, the paper reports the testing of a magnetorheological damper with an universal testing machine, for a set of frequency, amplitude, and current. A modified Bouc–Wen model considering the amplitude and input current dependence of the damper parameters has been proposed. It has been shown that the damper response can be satisfactorily predicted with this model. Second, a backstepping based nonlinear current monitoring of magnetorheological dampers for semi-active control of structures under earthquakes has been developed. It provides a stable nonlinear magnetorheological damper current monitoring directly based on system feedback such that current change in magnetorheological damper is gradual. Unlike other MR damper control techniques available in literature, the main advantage of the proposed technique lies in its current input prediction directly based on system feedback and smooth update of input current. Furthermore, while developing the proposed semi-active algorithm, the dynamics of the supplied and commanded current to the damper has been considered. The efficiency of the proposed technique has been shown taking a base isolated three story building under a set of seismic excitation. Comparison with widely used clipped-optimal strategy has also been shown.
Modeling of Cavitation Bubble Dynamics in Multicomponent Mixtures
Authors: Huang Si , Mohamad A. A.
Published: February 2009

Investigation on cavitation in multicomponent (solid-liquid and liquid-liquid) mixtures has many applications in the industries and engineering. In this paper, for simulation of multicomponent mixtures, a set of equations with first-order bubble-wall Mach number is derived for a single spherical bubble in quasihomogeneous mixtures. Cavitation bubble behaviors in several kinds of liquid-liquid and solid-liquid mixtures are numerically calculated based on the current model, including the temporal variations in the bubble radius, pressure, and temperature inside the bubble. Specifically, the analysis is focused on the impact of pressure and temperature, while the bubble collapses in the mixtures. The computed results are compared with the previously reported experimental ones to demonstrate the validity of the current model and the numerical procedures.
Hot-Wire Anemometry for Velocity Measurements in Nanopowder Flows
Authors: Bardakhanov Sergey P. , Joo Sang W.
Published: February 2009

A new technique for velocity-field measurements in fine granular systems is introduced. The hot-wire anemometry, mainly used for gaseous flows, is applied to nanopowders and is found to be a viable experimental method for flow measurements. A generic chute flow of aluminum oxide C and Aerosil A-90 and A-380 powders through a vertical channel is chosen as a test platform, and the results suggest that the hot-wire anemometry is a favorable option for nanopowder measurements.
Parameters for Assessing Oil Reservoir Water Flooding Additives
Authors: Reuvers Nico , Golombok Michael
Published: February 2009

This paper is concerned with deriving parameters for assessing the effectiveness of fluid additives to improve water flooding during enhanced oil recovery. We focus particularly on the use of rheological modifiers, which do not show monotonic behavior with the shear rate within the rock pores. We derive figures of merit based on (1) relative retardation in high and low permeability rock, (2) profile flattening, and (3) injectivity index. Only the last of these provides a measure of water flood profile improvement while maintaining sufficient fluid flow and production levels.
Intelligibility of interrupted sentences at subsegmental levels in young normal-hearing and elderly hearing-impaired listeners
Authors: Lee Jae Hee , Kewley-Port Diane
Published: February 2009

Although listeners can partially understand sentences interrupted by silence or noise, and their performance depends on the characteristics of the glimpses, few studies have examined effects of the types of segmental and subsegmental information on sentence intelligibility. Given the finding of twice better intelligibility from vowel-only glimpses than from consonants [Kewley-Port et al. (2007). “Contribution of consonant versus vowel information to sentence intelligibility for young normal-hearing and elderly hearing-impaired listeners,” J. Acoust. Soc. Am. 122, 2365–2375], this study examined young normal-hearing and elderly hearing-impaired (EHI) listeners’ intelligibility of interrupted sentences that preserved four different types of subsegmental cues (steady-states at centers or transitions at margins; vowel onset or offset transitions). Forty-two interrupted sentences from TIMIT were presented twice at 95dB SPL, first with 50% and second with 70% of sentence duration. Compared to high sentence intelligibility for uninterrupted sentences, interrupted sentences had significant decreases in performance for all listeners, with a larger decrease for EHI listeners. Scores for both groups were significantly better for 70% duration than for 50% but were not significantly different for the type of subsegmental information. Performance by EHI listeners was associated with their high-frequency hearing thresholds rather than with age. Together with previous results using segmental interruption, preservation of vowels in interrupted sentences provides greater benefit to sentence intelligibility compared to consonants or subsegmental cues.
Language experience and consonantal context effects on perceptual assimilation of French vowels by American-English learners of French
Authors: Levy Erika S.
Published: February 2009

Recent research has called for an examination of perceptual assimilation patterns in second-language speech learning. This study examined the effects of language learning and consonantal context on perceptual assimilation of Parisian French (PF) front rounded vowels /y/ and /œ/ by American English (AE) learners of French. AE listeners differing in their French language experience (no experience, formal instruction, formal-plus-immersion experience) performed an assimilation task involving PF /y, œ, u, o, i, ε, a/ in bilabial /rabVp/ and alveolar /radVt/ contexts, presented in phrases. PF front rounded vowels were assimilated overwhelmingly to back AE vowels. For PF /œ/, assimilation patterns differed as a function of language experience and consonantal context. However, PF /y/ revealed no experience effect in alveolar context. In bilabial context, listeners with extensive experience assimilated PF /y/ to ∕uj∕ less often than listeners with no or only formal experience, a pattern predicting the poorest /u-y/ discrimination for the most experienced group. An “internal consistency” analysis indicated that responses were most consistent with extensive language experience and in bilabial context. Acoustical analysis revealed that acoustical similarities among PF vowels alone cannot explain context-specific assimilation patterns. Instead it is suggested that native-language allophonic variation influences context-specific perceptual patterns in second-language learning.