bluuebunny/crossref_metadata_2025 huggingface dataset:
The origins of face perception: specific versus non‐specific mechanisms
Authors: Simion Francesca , Macchi Cassia Viola , Turati Chiara , Valenza Eloisa
Published: August 2002

Many studies have demonstrated that newborns prefer upright faces over upside‐down faces. Based on this evidence, some have suggested that faces represent a special class of stimuli for newborns and there is a qualitative difference between the processes involved in perception of facelike and non‐facelike patterns (i.e. structural hypothesis). Others suggest that there is no reason to suppose that faces are different from other patterns, because faces, like any other class of visual stimuli, are subject to filtering by the properties of the visual system (i.e. sensory hypothesis). The core question that will be addressed in the present paper is whether, to manifest itself, face preference requires the unique structure of the face, represented by the relative spatial location of its internal features, or rather some more general properties that other stimuli may also possess. Evidence will be presented supporting the idea that newborns do not respond to facelike stimuli by ‘facedness’ but, rather, by some general structural characteristics that best satisfy the constraints of the immature visual system. Copyright © 2001 John Wiley & Sons, Ltd.
Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer
Authors: Swinnen Johannes V. , Roskams Tania , Joniau Steven , Van Poppel Hein , Oyen Raymond , Baert Luc , Heyns Walter , Verhoeven Guido
Published: August 2002

The expression of fatty acid synthase (FAS), a key lipogenic enzyme and potential target for antineoplastic therapy, was analyzed in 87 frozen needle biopsies of prostate cancer using a highly sensitive immunohistochemical detection technique (Envision). In comparison to normal or benign, hyperplastic glandular structures, which were all negative for FAS staining, immunohistochemical signal was evident in 24/25 low grade prostatic epithelial neoplasia (PIN) lesions, in 26/26 high grade PIN lesions and in 82/87 invasive carcinomas. Staining intensity tended to increase from low grade to high grade PIN to invasive carcinoma. Cancers with a high FAS expression had an overall high proliferative index. No correlation was found between FAS expression and lipid accumulation. These findings indicate that increased FAS expression is one of the earliest and most common events in the development of prostate cancer, suggesting that FAS may be used as a general prostate cancer marker and that antineoplastic therapy based on FAS inhibition may be an option for chemoprevention or curative treatment for nearly all prostate cancers. © 2001 Wiley‐Liss, Inc.
Social class and risk of Hodgkin's disease in young‐adult women in 1988–94
Authors: Glaser Sally L. , Clarke Christina A. , Nugent Rebecca A. , Stearns Cynthia B. , Dorfman Ronald F.
Published: August 2002

Hodgkin's disease (HD) risk in young adults has been associated with higher childhood social class. Although recent decades have witnessed increases in both young‐adult HD incidence rates and the socioeconomic affluence reported to influence risk, social class risk factors have not been reexamined. For 204 cases and 254 controls aged 19–44 years from a population‐based case‐control study of HD diagnosed in 1988–94 in San Francisco area females, we evaluated social class predictors of HD overall and for subgroups defined by age and by ethnicity. HD was associated weakly with a few childhood social class markers but more strongly with combinations of these variables. Risk was higher for women with family‐owned than rented childhood homes; for US‐born women with single vs. shared bedrooms at age 11; and for women with 2+ births who were from smaller than larger childhood households. These patterns differed by age, with risk appearing to increase over the young‐adult years for some factors and to decrease for others. In whites, risk was additionally associated with having a single childhood bedroom in larger households, and with tall adult height in women from smaller childhood households. In nonwhites, risk was higher for single bedrooms at age 11 in smaller childhood households, taller height and higher maternal education. Most study findings support the hypothesis that HD development in young adults follows protection from early exposure to other children. Variation in risk by age suggests differing etiologies across young adulthood, or the importance of birth cohort‐appropriate social‐class measures. Negative findings for previously reported risk factors may reflect their insufficient heterogeneity of exposure or their failure to measure cohort‐relevant exposures in this population. © 2001 Wiley‐Liss, Inc.
Curcumin exerts multiple suppressive effects on human breast carcinoma cells
Authors: Shao Zhi‐Ming , Shen Zhen‐Zhou , Liu Can‐Hui , Sartippour Maryam R. , Go Vay Liang , Heber David , Nguyen Mai
Published: August 2002

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)‐positive MCF‐7 cells, being more pronounced in estrogen‐containing media and in the presence of exogenous 17‐β estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF‐β (transforming growth factor) in ER‐positive MCF‐7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)‐CAT activities induced by 17‐β estradiol. In addition, we demonstrate that curcumin exerts strong antiinvasive effects in vitro that are not estrogen dependent in the ER‐negative MDA‐MB‐231 breast cancer cells. These antiinvasive effects appear to be mediated through the downregulation of MMP‐2 (matrix metalloproteinase) and the upregulation of TIMP‐1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b‐FGF (basic fibroblast growth factor) mainly in ER‐negative MDA‐MB‐231 cells. © 2001 Wiley‐Liss, Inc.
Significance of the association between heparin‐binding epidermal growth factor‐like growth factor and CD9 in human gastric cancer
Authors: Murayama Yoko , Miyagawa Jun‐ichiro , Shinomura Yasuhisa , Kanayama Shuji , Isozaki Koji , Yamamori Katsumi , Mizuno Hitoshi , Ishiguro Shingo , Kiyohara Tatsuya , Miyazaki Yoshiji , Taniguchi Naoyuki , Higashiyama Shigeki , Matsuzawa Yuji
Published: August 2002

Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is a member of the EGF family. Juxtacrine activity of proHB‐EGF (the membrane‐anchored form of HB‐EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB‐EGF and CD9 are coexpressed in gastric cancer. HB‐EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB‐EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB‐EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB‐EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB‐EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB‐EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB‐EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner. © 2002 Wiley‐Liss, Inc.
Tumor‐targeted immune complex formation: Effects on myeloid cell activation and tumor‐directed immune cell migration
Authors: Kroesen Bart‐Jan , McLaughlin Pamela M.J. , Schuilenga‐Hut Petra H.L. , Jacobs Susan C. , Molema Grietje , Helfrich Wijnand , De Leij Lou F.M.H.
Published: August 2002

The effectiveness of cellular immunotherapy of solid tumors is often hampered by the lack of specific infiltration of immune effector cells into the tumor mass. Therefore, we studied the potential of tumor antigen‐specific antibodies to elicit tumor‐specific myeloid cell activation, to induce or enhance tumor infiltration by immune cells. To this end, we developed an in vitro model system using the human myeloid cell line MonoMac‐6. Incubation of IFN‐γ–primed MonoMac‐6 cells with serum‐opsonized zymosan or EGP‐2–directed, mouse IgG2a‐opsonized, EGP‐2‐positive tumor cells resulted in the production of ROS and TNF‐α and induced E‐selectin and ICAM‐1 expression on HUVECs. FcR‐mediated MonoMac‐6 cell activation was strictly dependent on the activation of MonoMac‐6 cells with IFN‐γ. In addition, no myeloid cell activation was observed in the presence of human serum or using tumor antigen‐specific mouse antibody subclasses other than IgG2a, suggesting the crucial involvement of CD64 (FcγR1) in the effects observed. However, serum‐inhibited myeloid cell activation was completely restored employing a 2‐step targeting approach in which tumor cell opsonization with mouse anti‐EGP‐2 antibodies was followed by incubation with human antimouse Ig antibodies. Moreover, using this 2‐step approach, not only anti‐EGP‐2–directed mouse IgG2a but also mouse IgG1 antibodies effectively induced tumor‐specific myeloid cell activation. In conclusion, we describe a method to induce efficient and tumor‐specific activation of myeloid cells based on the sequential use of mouse tumor antigen‐specific and human antimouse Ig antibodies. Targeted myeloid cell activation may provide a means to aid in the induction of a tumor‐directed immune response and as such, the method described here could be of clinical significance. © 2002 Wiley‐Liss, Inc.
Prognostic significance of Ep‐CAM AND Her‐2/neu overexpression in invasive breast cancer
Authors: Spizzo Gilbert , Obrist Peter , Ensinger Christian , Theurl Igor , Dünser Martina , Ramoni Angela , Gunsilius Eberhard , Eibl Günther , Mikuz Gregor , Gastl Günther
Published: August 2002

To assess the frequency and prognostic impact of Ep‐CAM and Her‐2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow‐up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep‐CAM and Her‐2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her‐2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep‐CAM and Her‐2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep‐CAM and Her‐2/neu overexpression were predictive for poor disease‐free (DFS) and disease‐related overall survival (DROS). Concurrent Ep‐CAM and Her‐2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her‐2/neu and Ep‐CAM overexpression. By multivariate analysis Ep‐CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her‐2/neu overexpression. In conclusion, overexpression of Ep‐CAM and Her‐2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories. © 2002 Wiley‐Liss, Inc.
Identification of cancer/testis genes by database mining and mRNA expression analysis
Authors: Scanlan Matthew J. , Gordon Claudia M. , Williamson Barbara , Lee Sang‐Yull , Chen Yao‐Tseng , Stockert Elisabeth , Jungbluth Achim , Ritter Gerd , Jäger Dirk , Jäger Elke , Knuth Alexander , Old Lloyd J.
Published: August 2002

Cancer/testis (CT) antigens are immunogenic proteins expressed predominantly in gametogenic tissue and cancer; they are considered promising target molecules for cancer vaccines. The identification of new CT genes is essential to the development of polyvalent cancer vaccines designed to overcome tumor heterogeneity and antigen loss. In the current study, a search for new CT genes was conducted by mining the Unigene database for gene clusters that contain expressed sequence tags derived solely from both normal testis and tumor‐derived cDNA libraries. This search identified 1,325 different cancer/testis‐associated Unigene clusters. The mRNA expression pattern of 73 cancer/testis‐associated Unigene clusters was assessed by reverse transcriptase polymerase chain reaction. Three gene products, CT15/Hs.177959, CT16/Hs.245431 and CT17/Hs.178062, were detected only in testis and in tumor tissue. CT15 is equivalent to ADAM2/fertilin‐β. CT16, an uncharacterized gene product, has homology (30–50%) to members of the GAGE gene family and is 89% identical to CT16.2/Hs.293317, indicating that CT16 and CT16.2 are members of a new GAGE gene family. The uncharacterized gene product, CT17, has homology (30%) to phospholipase A1. RT‐PCR analysis showed that CT15 is expressed exclusively in renal cancer, whereas CT16 and CT17 are expressed in a range of human cancers. Real‐time RT‐PCR analysis of newly defined CT genes and the prototype CT antigens, MAGE‐3 and NY‐ESO‐1, revealed low levels (less than 3% of the level detected in testis) of CT15, CT16 and NY‐ESO‐1 in a limited range of normal, non‐gametogenic tissues. This study demonstrates the merits of database mining with respect to the identification of tissue‐restricted gene products expressed in cancer. © 2002 Wiley‐Liss, Inc.
Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy
Authors: Siemann Dietmar W. , Mercer Emma , Lepler Sharon , Rojiani Amyn M.
Published: August 2002

The utility of combining the vascular targeting agents 5,6‐dimethyl‐xanthenone‐4 acetic acid (DMXAA) and combretastatin A‐4 disodium phosphate (CA4DP) with the anticancer drugs cisplatin and cyclophosphamide (CP) was evaluated in experimental rodent (KHT sarcoma), human breast (SKBR3) and ovarian (OW‐1) tumor models. Doses of the vascular targeting agents that led to rapid vascular shutdown and subsequent extensive central tumor necrosis were identified. Histologic evaluation showed morphologic damage of tumor cells within a few hours after treatment, followed by extensive hemorrhagic necrosis and dose‐dependent neoplastic cell death as a result of prolonged ischemia. Whereas these effects were induced by a range of CA4DP doses (10–150 mg/kg), the dose response to DMXAA was extremely steep; doses ≤ 15 mg/kg were ineffective and doses ≥ 20 mg/kg were toxic. DMXAA also enhanced the tumor cell killing of cisplatin, but doses > 15 mg/kg were required. In contrast, CA4DP increased cisplatin‐induced tumor cell killing at all doses studied. This enhancement of cisplatin efficacy was dependent on the sequence and interval between the agents. The greatest effects were achieved when the vascular targeting agents were administered 1–3 hr after cisplatin. When CA4DP (100 mg/kg) or DMXAA (17.5 mg/kg) were administered 1 hr after a range of doses of cisplatin or CP, the tumor cell kill was 10–500‐fold greater than that seen with chemotherapy alone. In addition, the inclusion of the antivascular agents did not increase bone marrow stem cell toxicity associated with these anticancer drugs, thus giving rise to a therapeutic gain. © 2002 Wiley‐Liss, Inc.
Intragenic amplification and formation of extrachromosomal small circular DNA molecules from the PIP gene on chromosome 7 in primary breast carcinomas
Authors: Autiero Monica , Camarca Alessandra , Ciullo Marina , Debily Marie‐Anne , El Marhomy Sandrine , Pasquinelli Rosa , Capasso Immacolata , D'Aiuto Giuseppe , Anzisi Anna Maria , Piatier‐Tonneau Dominique , Guardiola John
Published: August 2002

The PIP gene is expressed in exocrine glands and, in pathologic conditions, in breast cysts and breast cancers exhibiting apocrine features. It is localized on the long arm of chromosome 7, a region frequently alterated in mammary tumors. We previously described an abnormal restriction pattern of the PIP gene in 33% of prostate carcinomas analyzed. Here, we analyze the structure of the PIP gene in primary breast carcinomas. We report that part of the 3′ end, including exon 3, intron C, two‐thirds of exon 4 and a small portion of intron B, is amplified and involved in the formation of extrachromosomal spcDNA molecules in 3/14 (21.4%) breast cancers analyzed. The involvement of a well‐defined intragenic region of a gene in the formation of spcDNA appears to be unprecedented. Since spcDNA has been suggested to serve as an enhancer of genetic instability, the PIP gene may be the target of genomic variability processes in breast cancer. © 2002 Wiley‐Liss, Inc.
A model for stock return distribution
Authors: Linden Mikael
Published: August 2002

The Laplace mixture distribution for stock share returns is derived from conditional N(0, σ2) distribution. The conditioning variable, σ2, is assumed to be an exponentially distributed random variable. This offers a natural stochastic interpretation of the risk involved with the stock share. Maximum likelihood (ML) estimates for returns of the 20 most traded shares and the aggregate index of the Helsinki stock market in late 1980s do not reject the Laplace distribution model. The results extend to returns over longer periods than 1 day. Copyright © 2001 John Wiley & Sons, Ltd.
The non‐linear dynamics of output and unemployment in the U.S.
Authors: Altissimo Filippo , Violante Giovanni L.
Published: August 2002

This paper studies the joint dynamics of U.S. output and unemployment rate in a non‐linear VAR model. The non‐linearity is introduced through a feedback variable that endogenously augments the output lags of the VAR in recessionary phases. Sufficient conditions for the ergodicity of the model, potentially applying to a larger class of threshold models, are provided. The linear specification is rejected in favour of our threshold VAR. However, in the estimation the feedback is found to be statistically significant only on unemployment, while it transmits to output through its cross‐correlation. This feedback effect from recessions generates important asymmetries in the propagation of shocks, a possible key to interpret the divergence in the measures of persistence in the literature. The regime‐dependent persistence also explains the finding that the feedback from recession exerts a positive effect on the long‐run growth rate of the economy, an empirical validation of the Schumpeterian macroeconomic theories. Copyright © 2001 John Wiley & Sons, Ltd.
Engineering protein and cell adhesivity using PEO‐terminated triblock polymers
Authors: Liu Valerie A. , Jastromb William E. , Bhatia Sangeeta N.
Published: August 2002

Previous studies on customizing cell culture environments have utilized a variety of microfabrication‐based tools to control the spatial localization of adhesive proteins and subsequently mammalian cells. Others have used various methods to immobilize nonadhesive PEO‐based polymers on surfaces to inhibit protein absorption and cell adhesion. In this study, we report the application of a well‐characterized, commercially available, PEO‐terminated triblock polymer (Pluronic™ F108) to create micropatterned nonadhesive domains on a variety of biomaterials that deter cell adhesion for up to 4 weeks in culture. The Pluronic can be applied using microfluidic tools or photolithographic techniques, and can be adsorbed to a variety of common surfaces including tissue culture polystyrene, methylated glass, silicone, and polylactic‐co‐glycolic acid. The effectiveness of the Pluronic in inhibiting cell adhesion in the presence of collagen I is also quantified. Finally, these patterning techniques are generalized to control tissue organization on a variety of common biomaterials. This simple method for micropatterning PEO and, therefore, proteins and cells should prove useful as a tool for biomolecular surface engineering. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 126–134, 2002
Retention and activity of BMP‐2 in hyaluronic acid‐based scaffolds in vitro
Authors: Kim Hyun D. , Valentini Robert F.
Published: August 2002

Bone morphogenetic protein‐2 (BMP‐2) delivered in a suitable implantable matrix has the potential to repair local skeletal defects by inducing new bone formation from undifferentiated plurpotent stem cells resident in host tissue. In this study, we examined in vitro the potential of a derivatized hyaluronic acid (Hyaff‐11) scaffold as a delivery vehicle for recombinant human BMP‐2 (rhBMP‐2) in bone and cartilage repair therapies. Hyaff‐11 scaffolds were fabricated using a phase inversion/particulate leaching method and soak‐loaded with rhBMP‐2. In vitro release kinetics of rhBMP‐2, demonstrated using enzyme‐linked immunosorbant assay and alkaline phosphatase (ALP) assay revealed a slow, sustained rhBMP‐2 release during 28 days, with a cumulative release of 31.82% of the initial rhBMP‐2 loaded. rhBMP‐2 was released in bioactive form as demonstrated by ALP induction of pluripotent cell line, C3H10T1/2 (T1/2), down the osteoblast lineage when incubated with the release supernatants. rhBMP‐2 retention in Hyaff‐11 scaffolds was greater than that from collagen gels, which released most of the initially loaded rhBMP‐2 by 14 days. rhBMP‐2‐loaded Hyaff‐11 scaffolds were also seeded with T1/2 cells and evaluated at 3, 7, 14, and 28 days for viability and expression of osteoblast phenotype. Cells remained viable throughout the study and expressed a time‐ and dose‐dependent ALP and osteocalcin expression in the rhBMP‐2 groups. Based on these observations, Hyaff‐11 scaffolds may be suitable delivery systems for rhBMP‐2 in bone/cartilage repair because of their ability to retain rhBMP‐2, release low levels of bioactive rhBMP‐2 to the local environment in a sustained manner, and stimulate differentiation of pluripotent stem cells. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 573–584, 2002
Effect of elastin on the calcification rate of collagen‐elastin matrix systems
Authors: Singla Anuj , Lee Chi H.
Published: August 2002

The role of elastin in the aortic wall calcification and involved mechanisms were investigated. The major hypothesis of this work is that elastin is one of the major components to regulate calcification of bioprosthetic heart valve (BHV). The relationship between the elastin content and the calcification rate of the aortic wall was established using collagen‐elastin matrices (CEM) made of varying ratios of collagen and elastin (90 and 10, 50 and 50, and 20 and 80). Biophysical characterization of CEM was performed by water content measurement and the tensile strength test. The conformational changes of the calcifiable matrix were evaluated as a function of elastin content using Fourier transform infrared (FTIR) spectroscopy. The calcium contents in CEM implanted in the rat subcutaneous model for 7 days were measured using atomic absorption (AA) spectroscopy. As the concentration of elastin in CEM increased from 10 to 80%, the total amount of calcium accumulated in CEM also increased. The calcium level in CEM containing the collagen and an elastin ratio of 20:80 was 20.16 ± 0.70 μg/mg compared with 1.96 ± 0.04 μg/mg in CEM containing the collagen and an elastin ratio of 90:10. The calcification rate of CEM pretreated with ethanol increased, as the elastin concentration in the CEM. However, the calcification rate of CEM pretreated with ethanol is significantly lower than that of the untreated control. The permeation rate of ethanol through CEM with the collagen and an elastin ratio of 20:80 (0.37 ± 0.13 mmol/cm2/h) is significantly smaller than that through CEM with 90:10 (0.94 ± 0.27 mmol/cm2/h). These results indicate that elastin has a significant role in tissue calcification and that elastin's resistance to ethanol penetration partially contributes less effectiveness of ethanol on aortic wall calcification. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 368–374, 2002; DOI 10.1002/jbm.10077
Leukodepletion for acute lymphocytic leukemia in a three‐week‐old infant
Authors: Woloskie Sheryl , Armelagos Heidi , Meade J. Michael , Haas Debra
Published: August 2002

We report the smallest infant (4.5 kg) to receive leukapheresis as an immediate treatment for Infantile Acute Lymphocytic Leukemia. Leukodepletion helps prevent the risks of hyperviscosity and cerebrovascular and pulmonary leukostasis. In addition, it is a desirable precursor to chemotherapy to potentially reduce metabolic and renal complications associated with rapid cell lysis. Because of this infant's small size, she presented us with multiple concerns, including hypocalcemia from citrate anticoagulation, extracorporeal volume and fluid balance, inlet flow rates. and establishment of adequate interface. Our positive experience in performing this procedure suggests that cytapheresis is a feasible treatment even for very young infants. J. Clin. Apheresis. 16:31‐32, 2001. © 2001 Wiley‐Liss, Inc.
Cactus‐independent nuclear translocation of Drosophila RELISH
Authors: Cornwell William D. , Kirkpatrick Robert B.
Published: August 2002

Insects can effectively and rapidly clear microbial infections by a variety of innate immune responses including the production of antimicrobial peptides. Induction of these antimicrobial peptides in Drosophila has been well established to involve NF‐κB elements. We present evidence here for a molecular mechanism of Lipopolysaccharide (LPS)‐induced signaling involving Drosophila NF‐κB, RELISH, in Drosophila S2 cells. We demonstrate that LPS induces a rapid processing event within the RELISH protein releasing the C‐terminal ankyrin‐repeats from the N‐terminal Rel homology domain (RHD). Examination of the cellular localization of RELISH reveals that the timing of this processing coincides with the nuclear translocation of the RHD and the retention of the ankyrin‐repeats within the cytoplasm. Both the processing and the nuclear translocation immediately precede the expression of antibacterial peptide genes cecropin A1, attacin, and diptericin. Over‐expression of the RHD but not full‐length RELISH results in an increase in the promoter activity of the cecropin A1 gene in the absence of LPS. Furthermore, the LPS‐induced expression of these antibacterial peptides is greatly reduced when RELISH expression is depleted via RNA‐mediated interference. In addition, loss of cactus expression via RNAi revealed that RELISH activation and nuclear translocation is not dependent on the presence of cactus. Taken together, these results suggest that this signaling mechanism involving the processing of RELISH followed by nuclear translocation of the RHD is central to the induction of at least part of the antimicrobial response in Drosophila, and is largely independent of cactus regulation. J. Cell. Biochem. 82: 22–37, 2001. © 2001 Wiley‐Liss, Inc.
Green tea extracts decrease carcinogen‐induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture
Authors: Kavanagh Kathryn T. , Hafer Laurie J. , Kim Dong W. , Mann Koren K. , Sherr David H. , Rogers Adrianne E. , Sonenshein Gail E.
Published: August 2002

Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin‐3 gallate (EGCG), which possess anti‐oxidant qualities. Reduction of chemically induced mammary gland carcinogenesis by green tea in a carcinogen‐induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have tested the effects of green tea on mammary tumorigenesis using the 7,12‐dimethylbenz(a)anthracene (DMBA) Sprague‐Dawley (S‐D) rat model. We report that green tea significantly increased mean latency to first tumor, and reduced tumor burden and number of invasive tumors per tumor‐bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA‐MB‐231 estrogen receptor‐negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA‐transformed D3‐1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27Kip1 cyclin‐dependent kinase inhibitor (CKI) expression. Hs578T cells expressing elevated levels of p27Kip1 protein due to stable ectopic expression displayed increased G1 arrest. Thus, green tea had significant chemopreventive effects on carcinogen‐induced mammary tumorigenesis in female S‐D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27Kip1 CKI. J. Cell. Biochem. 82:387–398, 2001. © 2001 Wiley‐Liss, Inc.
Relation between the flexibility of the WPD loop and the activity of the catalytic domain of protein tyrosine phosphatase SHP‐1
Authors: Yang Jian , Niu Tianqi , Zhang Aihua , Mishra Ashwini K. , Zhao Zhizhuang Joe , Zhou G. Wayne
Published: August 2002

The conserved WPD loop of protein tyrosine phosphatases play an important role in the catalytic activity and the invariant aspartate residue acts as a general acid/base catalyst in the dephosphorylation reaction. In our previous report, we have demonstrated that the catalytic activities of the PTPs are influenced by the flexibility and stability of the WPD loop in its active “open” conformation [Yang et al., 1998]. Phosphatases with a more flexible WPD loop generally have higher specific activity. In this report, we modify the WPD loop of SHP‐1 by alanine‐scan mutation of the residues flanking the loop and measure their effects on the catalytic activity of the phosphatase. We show that the S418A, V424A, S426A, E427A, and P428A mutants increase the phosphatase activity, possibly due to the increased flexibility of the WPD loop, whereas the L417A, L417G and P425A mutants decrease its phosphatase activity. In addition, we propose that the two‐proline residues in the WPD loop (Pro420 and Pro425 in SHP‐1) work as pivotal points through a conserved hydrophobic network and allows residues between the pivotal points to have maximum flexibility in enhancing the phosphatase activity. Furthermore, our data suggest that the hydrolysis of the phosphoryl‐cysteine intermediate, not its formation, is the rate‐limiting step with p‐nitrophenyl phosphate as the substrate while both the steps are rate‐limiting with phosphotyrosine as the substrate. J. Cell. Biochem. 84: 47–55, 2002. © 2001 Wiley‐Liss, Inc.
Quantum mechanical study of the conformational behavior of proline and 4R‐hydroxyproline dipeptide analogues in vacuum and in aqueous solution
Authors: Benzi Caterina , Improta Roberto , Scalmani Giovanni , Barone Vincenzo
Published: August 2002

The conformational behavior of the title compounds has been investigated by Hartree–Fock, MP2, and DFT computations on the most significant structures related to variations of the backbone dihedral angles, cis/trans isomerism around the peptide bond, and diastereoisomeric puckering of the pyrrolidine ring. In vacuum the reversed γ turn (γl), characterized by an intramolecular hydrogen bridge, corresponds to the absolute energy minimum for both puckerings (up and down) of the pyrrolidine ring. An additional energy minimum is found in the helix region, but only for an up puckering of the pyrrolidine ring. When solvent effects are included by means of the polarizable continuum model the conformer observed experimentally in condensed phases becomes the absolute minimum. The down puckering is always favored over its up counterpart, albeit by different amounts (0.4–0.5 kcal/mol for helical structures and about 2 kcal/mol for γl structures). In helical structures cis arrangements of the peptide bond are only slightly less stable than their trans counterparts. This is no longer true for γl structures, because the formation of an intramolecular hydrogen bond is possible only for trans peptide bonds. In most cases, proline and hydroxyproline show the same general trends; however, the electronegative 4(R) substituent of hydroxyproline leads to a strong preference for up puckerings irrespective of the backbone conformation. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 341–350, 2002
Identifying native‐like protein structures using physics‐based potentials
Authors: Dominy Brian N. , Brooks, Charles L.
Published: August 2002

As the field of structural genomics matures, new methods will be required that can accurately and rapidly distinguish reliable structure predictions from those that are more dubious. We present a method based on the CHARMM gas phase implicit hydrogen force field in conjunction with a generalized Born implicit solvation term that allows one to make such discrimination. We begin by analyzing pairs of threaded structures from the EMBL database, and find that it is possible to identify the misfolded structures with over 90% accuracy. Further, we find that misfolded states are generally favored by the solvation term due to the mispairing of favorable intramolecular ionic contacts. We also examine 29 sets of 29 misfolded globin sequences from Levitt's “Decoys ‘R’ Us” database generated using a sequence homology‐based method. Again, we find that discrimination is possible with approximately 90% accuracy. Also, even in these less distorted structures, mispairing of ionic contacts results in a more favorable solvation energy for misfolded states. This is also found to be the case for collapsed, partially folded conformations of CspA and protein G taken from folding free energy calculations. We also find that the inclusion of the generalized Born solvation term, in postprocess energy evaluation, improves the correlation between structural similarity and energy in the globin database. This significantly improves the reliability of the hypothesis that more energetically favorable structures are also more similar to the native conformation. Additionally, we examine seven extensive collections of misfolded structures created by Park and Levitt using a four‐state reduced model also contained in the “Decoys ‘R’ Us” database. Results from these large databases confirm those obtained in the EMBL and misfolded globin databases concerning predictive accuracy, the energetic advantage of misfolded proteins regarding the solvation component, and the improved correlation between energy and structural similarity due to implicit solvation. Z‐scores computed for these databases are improved by including the generalized Born implicit solvation term, and are found to be comparable to trained and knowledge‐based scoring functions. Finally, we briefly explore the dynamic behavior of a misfolded protein relative to properly folded conformations. We demonstrate that the misfolded conformation diverges quickly from its initial structure while the properly folded states remain stable. Proteins in this study are shown to be more stable than their misfolded counterparts and readily identified based on energetic as well as dynamic criteria. In summary, we demonstrate the utility of physics‐based force fields in identifying native‐like conformations in a variety of preconstructed structural databases. The details of this discrimination are shown to be dependent on the construction of the structural database. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 147–160, 2002
Thermodynamics and kinetics of initial gas phase reactions in chemical vapor deposition of titanium nitride. Theoretical study of TiCl4 ammonolysis
Authors: Umanskii Stanislav Ya. , Novoselov Konstantin P. , Minushev Airat Kh. , Siodmiak Magdalena , Frenking Gernot , Korkin Anatoli A.
Published: August 2002

Thermodynamic equilibrium and kinetics of the gas‐phase reaction between TiCl4 and NH3 have been studied computationally using results from recent quantum mechanical calculations of titanium tetrachloride ammonolysis.1 These calculations were based upon the transition state theory for the direct reactions and RRKM theory for the reactions proceeding via intermediate complex. Rate constants for the barrierless reactions were expressed through the thermodynamic characteristics of the reagents and products using a semiempirical variational method. The kinetic simulation of the gas‐phase steps of CVD was performed within a model of a well‐stirred reactor at temperatures 300–1200 K and residence times between 0.1–2 s. At temperatures below 450 K formation of donor–acceptor complexes between TiCl4 and NH3 is the dominating process. At higher temperatures sequential direct ammonolysis takes place. At typical LPCVD conditions the only product of the first step of ammonolysis, TiCl3NH2, is formed in substantial amount. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1366–1376, 2001
The elastic net algorithm and protein structure prediction
Authors: Ball Keith D. , Erman Burak , Dill Ken A.
Published: August 2002

Predicting protein structures from their amino acid sequences is a problem of global optimization. Global optima (native structures) are often sought using stochastic sampling methods such as Monte Carlo or molecular dynamics, but these methods are slow. In contrast, there are fast deterministic methods that find near‐optimal solutions of well‐known global optimization problems such as the traveling salesman problem (TSP). But fast TSP strategies have yet to be applied to protein folding, because of fundamental differences in the two types of problems. Here, we show how protein folding can be framed in terms of the TSP, to which we apply a variation of the Durbin–Willshaw elastic net optimization strategy.1 We illustrate using a simple model of proteins with database‐derived statistical potentials and predicted secondary structure restraints. This optimization strategy can be applied to many different models and potential functions, and can readily incorporate experimental restraint information. It is also fast; with the simple model used here, the method finds structures that are within 5–6 Å all‐Cα‐atom RMSD of the known native structures for 40‐mers in about 8 s on a PC; 100‐mers take about 20 s. The computer time τ scales as τ∼n, where n is the number of amino acids. This method may prove to be useful for structure refinement and prediction. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 77–83, 2002
A comparison of the short and long forms of the Multiple Affect Adjective Check List—Revised (MAACL‐R)
Authors: Lubin Bernard , Van Whitlock Rodney , Reddy Deepika , Petren Suzanne
Published: August 2002

Brief, reliable, and valid assessment instruments are very important for clinical psychology research and practice. The possible equivalency of a short form and the long form of the Multiple Affect Adjective Check List—Revised (MAACL‐R; Zuckerman & Lubin,1985) was studied by correlating both forms of the MAACL‐R with the State Trait Personality Inventory (Spielberger,1995); the Affect Balance Scale (Bradburn,1969); and the Sensation Seeking Scale (Zuckerman,1978). Reliability and validity of the two forms were equivalent. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 411–416, 2001.
Exercise in treating depression: Broadening the psychotherapist's role
Authors: Pollock Kenneth M.
Published: August 2002

Research findings over the past two decades strongly indicate that moderate exercise can have a beneficial effect upon depression, yet suggestions to depressed patients that they exercise rarely are followed. Despite the research, few psychotherapists employ exercise promotion and maintenance as part of their treatment. An approach to integrating exercise promotion into psychotherapy treatment is presented. It incorporates a therapist–patient collaborative process involving joint assessment of biopsychosocial barriers and facilitators for exercise initiation and maintenance that are unique to the patient. Based upon the assessment, a collaborative exercise plan is developed and implemented. © 2001 John Wiley & Sons, Inc. J Clin Psychol/In Session 57: 1289–1300, 2001.
Heterogeneity of the signal transduction pathways for VEGF‐induced MAPKs activation in human vascular endothelial cells
Authors: Yashima Rei , Abe Mayumi , Tanaka Katsuhiro , Ueno Hikaru , Shitara Kenya , Takenoshita Seiichi , Sato Yasufumi
Published: August 2002

Vascular endothelial growth factor (VEGF) activates ERK and p38 MAPK in endothelial cells (ECs). The present study was aimed to compare its intracellular signal transduction pathways between three primary cultures of human ECs including human aortic ECs (HAECs), human umbilical vein ECs (HUVECs), and human microvascular ECs (HMVECs). VEGF activated ERK and p38 MAPK in all of three ECs. Isoforms of p38 MAPK that were activated by VEGF in HUVECs were p38‐α and p38‐δ. GF109203X, a specific inhibitor of PKC, markedly inhibited VEGF‐induced activation of ERK and p38 MAPK in HAECs and HUVECs, whereas it exhibited little effect in HMVECs. In contrast, dominant negative mutant of Ha‐Ras almost completely abrogated VEGF‐induced activation of ERK and p38 MAPK in HMVECs. Although dominant negative mutant of Ha‐Ras substantially inhibited the basal activities of ERK and p38 MAPK, it exhibited marginal effect on VEGF‐induced activation of ERK and p38 MAPK in HUVECs and HAECs. The activation of Ras by VEGF appeared to be most prominent in HMVECs. These results indicate that intracellular signal transduction pathways for VEGF‐induced activation of MAPKs are heterogeneous and vary depending on the origin of ECs.© 2001 Wiley‐Liss, Inc.
Oxidation of several chlorophenolic derivatives by UV irradiation and hydroxyl radicals
Authors: Benitez F Javier , Beltran‐Heredia Jesus , Acero Juan L , Rubio F Javier
Published: August 2002

The oxidation of some chlorophenols: 4‐chlorophenol, 2,4‐dichlorophenol, 2,4,6‐trichlorophenol, 2,3,4,6‐tetrachlorophenol, tetrachlorocatechol (3,4,5,6‐tetrachloro‐2‐hydroxy phenol) and 4‐chloroguaiacol (4‐chloro‐2‐methoxy phenol) has been studied via single photodecomposition produced by polychromatic UV irradiation, oxidation by hydroxyl radicals generated by Fenton's reagent (hydrogen peroxide plus ferrous ions), and degradation by hydroxyl radicals produced by combinations of UV irradiation plus hydrogen peroxide, and UV irradiation plus hydrogen peroxide and ferrous ions (photo‐Fenton system). These organics have been selected as models of chloro‐phenolic derivative pollutants present in wastewaters and groundwaters. The degradation levels obtained in each process are reported. The quantum yields in the single photodecomposition reaction and the rate constants between the chlorophenols and the hydroxyl radicals in the reaction with Fenton's reagent are determined. Finally, the additional contributions to the photodecomposition promoted by the radical reaction in the combined UV/H2O2 and photo‐Fenton systems are also evaluated.

© 2001 Society of Chemical Industry
Effect of amino acids containing sulfur on the corrosion of mild steel in phosphoric acid solutions polluted with Cl−, F− and Fe3+ ions–behaviour near and at the corrosion potential
Authors: Morad Mohamed Samir S , Hermas Abo El‐Hagag A , Aal Mohamed S Abdel
Published: August 2002

Research on non‐toxic inhibitors is of considerable interest in investigations into the replacement of hazardous classical molecules. This paper reports the action of four amino acids containing sulfur on the corrosion of mild steel in phosphoric acid solution with and without Cl−, F− and Fe3+ ions near and at the corrosion potential (Ecorr) using both the polarization resistance method and electrochemical impedance spectroscopy (EIS). Both cysteine and N‐acetylcysteine (ACC) showed higher inhibition efficiency than methionine and cystine. Adsorption of methionine onto a mild steel surface obeys the Frumkin adsorption isotherm and has a free energy of adsorption value (ΔG °ads) lower than those obtained in the presence of cystine, cysteine and ACC whose adsorption isotherms follow that of Langmuir. Both F− and Fe3+ ions stimulate mild steel corrosion while Cl− ions inhibit it. The binary mixtures of methionine, cysteine or ACC with Cl− or F− ions are effective inhibitors (synergism) while the combinations of the amino acid with Fe3+ or the ternary Cl−/F−/Fe3+ mixture have low inhibitive action (antagonism). EIS measurements revealed that the charge transfer process mainly controls the mechanism of mild steel corrosion in phosphoric acid solution in the absence and presence of the investigated additives. The mechanism of corrosion inhibition or acceleration is discussed.

© 2002 Society of Chemical Industry
Production of L‐methionine by immobilized pellets of Aspergillus oryzae in a packed bed reactor
Authors: Yuan Ying‐Jin , Wang Shu‐hao , Song Zheng‐xiao , Gao Rui‐chang
Published: August 2002

Production of L‐methionine by immobilized pellets of Aspergillus oryzae in a packed bed reactor was investigated. Based on the determination of relative enzymatic activity in the immobilized pellets, the optimum pH and temperature for the resolution reaction were 8.0 and 60 °C, respectively. The effects of substrate concentration on the resolution reaction were also investigated and the kinetic constants (Km and Vm) of immobilized pellets were found to be 7.99 mmol dm−3 and 1.38 mmol dm−3 h−1, respectively. The maximum substrate concentration for the resolution reaction without inhibition was 0.2 mol dm−3. The L‐methionine conversion rate reached 94% and 78% when substrate concentrations were 0.2 and 0.4 mol dm−3, respectively, at a flow rate of 7.5 cm3 h−1 using the small‐scale packed bed reactor developed. The half‐life of the L‐aminoacylase in immobilized pellets was 70 days in continuous operation. All the results obtained in this paper exhibit a practical potential of using immobilized pellets of Aspergillus oryzae in the production of L‐methionine.

© 2002 Society of Chemical Industry