bluuebunny/crossref_metadata_2025 huggingface dataset:
A fully 3D finite element model for non‐hydrostatic coastal flows with a free surface
Authors: Blasco Jordi , Maidana M. Augusto , Espino Manuel
Published: September 2008

In this paper we develop a finite element model, named HELIKE, for the numerical simulation of 3D, non‐hydrostatic, turbulent flows with a free surface like those arising from the study of the motion of water in coastal regions. The kinematic free‐surface equation is used to compute the surface elevation, without resorting to vertical averages. The model presented here incorporates surface wind stress, bottom friction and Coriolis acceleration, and it is applicable to irregular bottom topographies. A pressure stabilization technique is employed to stabilize the finite element solution. Numerical results obtained both in test problems and in a real‐life application confirm the accuracy, robustness and applicability of the proposed method. Copyright © 2008 John Wiley & Sons, Ltd.
Oral histoplasmosis: An unusual presentation
Authors: Narayana Nagamani , Gifford Ryan , Giannini Peter , Casey John
Published: September 2008

Background.

Histoplasmosis is a localized or systemic fungal infection which may present as an acute primary or “reactivation” infection in the setting of immunosuppression. Tumor necrosis factor alpha (TNF‐α) antagonists, used in the management of rheumatoid arthritis and Crohn disease, have been linked to reactivation of quiescent histoplasmosis. Microscopically, granulomas are either not evident or are infrequent in histoplasmosis when associated with TNF antagonist therapy presumably due to the suppression of macrophage activity.

Methods and Results.

This article describes an unusual presentation of oral histoplasmosis in a 75‐year‐old‐woman patient on TNF‐α antagonist, namely infliximab. Microscopically, cellular atypia resulted in a work‐up to rule out lymphoma. Gomori's methenamine silver stain demonstrated Histoplasma capsulatum leading to a diagnosis of histoplasmosis. She was treated successfully with itraconozole.

Conclusion.

This is the first reported case, insofar as the authors are able to determine, of oral histoplasmosis, in a patient undergoing treatment with infliximab. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Comparison of ultrasound‐guided core‐needle biopsy and fine‐needle aspiration in the assessment of head and neck lesions
Authors: Kraft Marcel , Laeng Hubert , Schmuziger Nicolas , Arnoux André , Gürtler Nicolas
Published: September 2008

Background.

Core‐needle biopsy (CNB) has been successfully applied in other medical specialties, but its value is undetermined in otolaryngology.

Methods.

This prospective study includes 75 patients, who were seen at our institution with a cervical mass. The results of CNB were compared with those of fine‐needle aspiration (FNA) in the 68 histologically verified cases.

Results.

CNB was superior to FNA providing a specific diagnosis (90% vs 66%) and achieved a higher accuracy in identifying true neoplasms (100% vs 93%) and detecting malignancy (99% vs 90%). However, the sensitivity and specificity did not differ significantly between both methods.

Conclusions.

Sonography and if necessary FNA should continue to be the investigation method of first choice for head and neck lesions. The main indication for CNB is after repeated failures of FNA to provide a diagnosis. It can also be performed in patients who are not surgical candidates or in those who refuse surgery. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Nodal metastases at level IIb during neck dissection for head and neck cancer: Clinical and pathologic evaluation
Authors: Santoro Roberto , Franchi Alessandro , Gallo Oreste , Burali Giulia , de' Campora Enrico
Published: September 2008

Background.

Selective neck dissection as a part of an elective or therapeutic treatment of the neck is a common practice during the surgical treatment of patients with head and neck cancer. Recently, the need for routine dissection of level IIb has been discussed. The aim of this study was to verify the incidence of metastases at level IIb in patients with clinically negative necks (N0) and clinically positive necks (N+) and discuss the need for its excision.

Methods.

A total of 114 patients with head and neck cancer undergoing neck dissection were prospectively analyzed. The total number of neck dissections analyzed was 148. The surgical specimens from each node level of the neck were pathologically diagnosed, with special attention to level IIb. Univariate associations between N classification and IIb positive cases were assessed using logistic regression and between IIa and IIb positive cases using Fisher exact test.

Results.

Of 148 neck dissections performed, level IIb resulted positive in 5 cases (3.3%): 1 patient with laryngeal cancer, 1 patient with oral cavity cancer, and 2 patients with oropharyngeal cancer, of which 1 underwent bilateral neck dissection. According to clinical N classification, for N0 and N+ the incidence of positive level IIb was 2% and 5%, respectively. All the cases with metastases at level IIb also showed metastases at level IIa. A statistically significant association between the presence of nodal metastases at level IIb and those at level IIa (p <.001) was found. The statistical association between N classification and IIb positive nodes only showed a trend toward significance (p = .06).

Conclusions.

The incidence of metastases at level IIb is low, also in the N+ necks, therefore dissection of this level could be unnecessary in N0 necks. Furthermore, an interesting statistical association between the presence of metastases at level IIb and at level IIa was recorded. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Diabetes insipidus and panhypopituitarism due to intrasellar metastasis from medullary thyroid cancer
Authors: Santarpia Libero , Gagel Robert F. , Sherman Steven I. , Sarlis Nicholas J. , Evans Douglas B. , Hoff Ana O.
Published: September 2008

Background.

Medullary thyroid cancer (MTC) commonly metastasizes to lymph nodes in the central and lateral neck, but spread to distant organs also occurs, typically involving lung, liver, and bone. Metastases to pituitary gland are rare for this tumor.

Methods.

We describe an unusual case and peculiar presentation of pituitary metastasis from MTC. We report clinical, genetic, and laboratory data of this patient.

Results.

A young woman with multiple endocrine neoplasia type 2B was seen with recent onset of classic symptoms and signs of panhypopituitarism, mild diabetes insipidus, and optic chiasmatic compression. Transphenoidal resection of an intrapituitary mass confirmed the presence of metastatic MTC.

Conclusions.

MTC recurrence may present solely with subacute pituitary symptomatology, even in the context of a very lengthy interval after initial surgery, atypically low calcitonin plasma levels, carcinoembryonic antigen doubling times, and the concomitant absence of other tell‐tale signs of disseminated metastatic disease. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
The role of algorithm and result comprehensibility of automated scheduling on complacency
Authors: Cegarra Julien , Hoc Jean‐Michel
Published: September 2008

Several studies have stressed that even expert operators who are aware of a machine's limits could adopt its proposals without questioning them (i.e., the complacency phenomenon). In production scheduling for manufacturing, this is a significant problem, as it is often suggested that the machine be allowed to build the production schedule, confining the human role to that of rescheduling. This article evaluates the characteristics of scheduling algorithms on human rescheduling performance, the quality of which was related to complacency. It is suggested that scheduling algorithms be characterized as having result comprehensibility (the result respects the scheduler's expectations in terms of the discourse rules of the information display) or algorithm comprehensibility (the complexity of the algorithm hides some important constraints). The findings stress, on the one hand, that result comprehensibility is necessary to achieve good production performance and to limit complacency. On the other hand, algorithm comprehensibility leads to poor performance due to the very high cost of understanding the algorithm. © 2008 Wiley Periodicals, Inc.
Comparing stationary standing with an intermittent walking posture during assembly operations
Authors: Balasubramanian Venkatesh , Adalarasu Kanagasabai , Regulapati Rahul
Published: September 2008

The purpose of this investigation was to evaluate two different standing postures, intermittent walking (dynamic) and stationary, on 11 volunteers. While performing the activity in a stationary posture, volunteers worked barefoot for 25 minutes at a particular workstation, taking up to five passive breaks. The dynamic standing postural activity was similar in every respect with the exception of the nature of the breaks that were spent walking from one workstation to the other. Foot pressure was analyzed using a static evaluation variable (contact area) and a dynamic evaluation variable (area pressure change root mean square [aPcrms]). Foot center of pressure (COP) was analyzed using two of its features: excursion length (LEN) and root mean square velocity of excursions (VEL). In addition, a psychophysical study was used to distinguish the comfort levels of various muscles between the two postures. The quantifications of the four physiological variables revealed a lower comfort index (p < 0.05) in stationary standing compared to dynamic standing during assembling duties. This significant distinction was further corroborated by the results of the psychophysical test. Such a positive influence of the dynamic standing posture on standing comfort can be used to improve industrial productivity. © 2008 Wiley Periodicals, Inc.
Method to improve the mitigative effectiveness of a series of check dams against debris flows
Authors: Osti Rabindra , Egashira Shinji
Published: September 2008

The advance of technology has led to more competent countermeasures, but lives and properties still continue to suffer from water‐induced disasters, such as floods, landslides, and debris flows. To increase the effectiveness of counter systems, improved methods of planning and designing such systems are prerequisite. This paper describes briefly a methodological approach for predicting debris flow characteristics, and proposes techniques for evaluating and improving the mitigative effectiveness of check dams against debris flows in steep mountain torrents. Additionally, a non‐dimensional parameter, namely potential storage volume, is introduced to generalize the evaluation processes. As an example, the 1999 debris‐flow event in the San Julian River, Venezuela, is chosen for discussion. The paper also proposes a method of evaluating the control function of a series of check dams as well as the criteria for the selection of their sizes, numbers and locations. It is hoped that this work will help to determine which combinations of check dams will fit best together for the optimal control of debris flows and available resources in any river basin. Copyright © 2008 John Wiley & Sons, Ltd.
A two‐dimensional inverse model to identify transmissivity in an anisotropic aquifer
Authors: Wu Shih‐Ching , Tan Yih‐Chi , Chen Chu‐Hui , Lin Shien‐Tsung , Ke Kai‐Yuan
Published: September 2008

This study suggested a numerical model using the Tabu search algorithm along with the Adjoint State method to identify the hydrogeological characteristics of an anisotropic groundwater aquifer. The Tabu search algorithm was applied to identify the anisotropic transmissivity components to avoid a local optimum. Then, the Adjoint State method was used to calculate the sensitivity of the parameters in order to increase the efficiency of the optimization. For an anisotropic and homogeneous aquifer, results showed that the optimal procedure presented combining the Tabu search algorithm and the Adjoint State method might successfully identify the values of the transmissivity components. If the duration of the pumping test was long enough (12‐h pumping test), the value of the transmissivity components could be optimized with type‐curve, straight‐line, and Tabu search methods, along with the Adjoint State methods. If the duration of the pumping test was short (0·5‐h pumping test), the Tabu search method, along with the Adjoint State method proposed herein, might successfully optimize the transmissivity components. For an anisotropic but heterogeneous aquifer, results showed that the suggested optimal procedure still successfully identified the values of the transmissivity components. Copyright © 2008 John Wiley & Sons, Ltd.
Biophysical and biochemical characterization of a liposarcoma‐derived recombinant MnSOD protein acting as an anticancer agent
Authors: Mancini Aldo , Borrelli Antonella , Schiattarella Antonella , Aloj Luigi , Aurilio Michela , Morelli Franco , Pica Alessandra , Occhiello Antonella , Lorizio Roberto , Mancini Roberto , Sica Alessandro , Mazzarella Lelio , Sica Filomena , Grieco Paolo , Novellino Ettore , Pagnozzi Daniela , Pucci Piero , Rommelaere Jean
Published: September 2008

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild‐type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N‐terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium‐labelled synthetic peptide. The labelled peptide permeated MCF‐7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I‐ and 131I‐labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro‐apoptotic mechanism. © 2008 Wiley‐Liss, Inc.
Original triazine inductor of new specific molecular targets, with antitumor activity against nonsmall cell lung cancer
Authors: Moreau Dimitri , Jacquot Catherine , Tsita Polyxeni , Chinou Ioanna , Tomasoni Cristophe , Juge Marcel , Antoniadou‐Vyza Ekaterini , Martignat Lionel , Pineau Alain , Roussakis Christos
Published: September 2008

Despite our growing insight into carcinogenesis, treatment of tumors, especially nonsmall cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. Drug discovery efforts have historically focused on the search for compounds that modulate the protein products of genes. Current drug therapy targets only a few hundred endogenous targets, mainly proteins, such as receptors and enzymes. But now, the interest in specifically targeting RNA is increasing, both for target validation and/or therapeutic purposes. In this regard, our work was concerned with the induction of new molecular targets correlated to a cytostatic effect on NSCLC cell line, after treatment with a new triazin named A190. The in vitro study of cell cycle and apoptosis induction demonstrated the antiproliferative potential of this new compounds, and the use of quantitative RT‐PCR analysis permit to display an original mechanism of action involving 2 genes: HEF1 and B2. The antitumor effect was also confirmed by the good results in vivo on nude mice xenografts. © 2008 Wiley‐Liss, Inc.
MicroRNA alterations in head and neck squamous cell carcinoma
Authors: Chang Steven S. , Jiang Wei Wen , Smith Ian , Poeta Luana M. , Begum Shahnaz , Glazer Chad , Shan Shannon , Westra William , Sidransky David , Califano Joseph A.
Published: September 2008

MicroRNAs (mirs) are small noncoding RNA molecules (∼22 nucleotides) that regulate posttranscriptional gene expression. Currently, there has not been a comprehensive study of their role in primary head and neck squamous cell carcinoma (HNSCC). To determine the role of mirs in HNSCC, we screened for altered microRNA expression in HNSCC primary tissue and cell lines. We then further tested the functional impact of alterations of specific mirs. An initial screening of 4 primary HNSCC, 4 normal mucosal controls and 4 HNSCC cell lines was analyzed for mature microRNA expression by microarray. Significance was determined using significance analysis of microarrays (SAM). Nine microRNAs were found by SAM to be upregulated or downregulated in tumor tissue including mir‐21, let‐7, 18, 29c, 142‐3p, 155, 146b (overexpressed) and 494 (underexpressed). Mir‐21 was validated by qRT‐PCR. Functional validation by growth assays was performed, further validating mir‐21. Transfection of mir‐21 into JHU‐011 and JHU‐012 cell lines showed a 39% increase in cell growth at 72 hr relative to controls (p < 0.05). Transfection of the inhibitor into JHU‐O12 cell lines showed a 92% decrease in cell growth relative to controls at 72 hr (p < 0.05). In addition, flow cytometry analysis of JHU‐012 cells 48 hr after mir‐21 inhibitor transfection showed a statistically significant increase in cytochrome c release and increased apoptosis. These differentially expressed microRNAs may be of interest as potential novel oncogenes and tumor suppressor genes in HNSCC. Mir‐21 is a putative oncogenic microRNA in head and neck cancer. © 2008 Wiley‐Liss, Inc.
Distinct CpG island methylation profiles and BRAF mutation status in serrated and adenomatous colorectal polyps
Authors: Kim Yong Ho , Kakar Sanjay , Cun Lisa , Deng Guoren , Kim Young S.
Published: September 2008

A subset of colorectal cancers with CpG island methylator phenotype‐high (CIMP‐H) is frequently associated with MSI and BRAF V600E mutation. Since limited data are available on different histological types of colorectal polyps, we compared the pattern and the frequency of promoter methylation, CIMP‐H, MSI, KRAS and BRAF V600E mutations and the relationship among these molecular parameters and the clinicopathologic characteristics in 110 serrated polyps (48 hyperplastic polyps, 32 sessile serrated adenomas and 30 serrated adenomas) and 32 tubular adenomas using 7 commonly used tumor‐associated gene loci. No significant difference in the frequency of overall methylation frequency (86% vs. 100%) and CIMP‐H (39% vs. 28%) between serrated polyps and tubular adenomas was observed, but proximally located serrated polyps showed more frequent methylation at 5 of 7 loci examined, and were more likely to be CIMP‐H (62% vs. 22%). MGMT methylation was more common in tubular adenomas while MLH1 and HIC1 were more frequently methylated in serrated polyps. BRAF mutation was frequently present in all types of serrated polyps (80%), but was absent in tubular adenomas and was not associated with CIMP or MSI status. These results show comparable frequencies of promoter methylation of tumor‐associated genes and CIMP‐H, but distinct differences in gene‐specific or colonic site‐specific methylation profiles occur in serrated polyps and tubular adenomas. BRAF mutation occurs independently of CIMP and MSI in all types of serrated polyps and may serve as a marker of serrated pathway of colorectal carcinogenesis. © 2008 Wiley‐Liss, Inc.
A panel of p16INK4A, MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma
Authors: Hoevenaars Brigiet M. , van der Avoort Irene A.M. , de Wilde Peter C.M. , Massuger Leon F.A.G. , Melchers Willem J.G. , de Hullu Joanne A. , Bulten Johan
Published: September 2008

Two pathways leading to vulvar squamous cell carcinoma (SCC) exist. The expression of proliferation‐ and cell‐cycle‐related biomarkers and the presence of high‐risk (hr) HPV might be helpful to distinguish the premalignancies in both pathways. Seventy‐five differentiated vulvar intra‐epithelial neoplasia (VIN)‐lesions with adjacent SCC and 45 usual VIN‐lesions (32 solitary and 13 with adjacent SCC) were selected, and tested for hr‐HPV DNA, using a broad‐spectrum HPV detection/genotyping assay (SPF10‐LiPA), and the immunohistochemical expression of MIB1, p16INK4A and p53. All differentiated VIN‐lesions were hr‐HPV‐ and p16‐negative and in 96% MIB1‐expression was confined to the parabasal layers. Eighty‐four percent exhibited high p53 labeling indices, sometimes with parabasal extension. Eighty percent of all usual VIN‐lesions were hr‐HPV‐positive, p16‐positive, MIB1‐positive and p53‐negative. Five (of seven) HPV‐negative usual VIN lesions, had an expression pattern like the other HPV‐positive usual VIN lesions. In conclusion, both pathways leading to vulvar SCC have their own immunohistochemical profile, which can be used to distinguish the 2 types of VIN, but cannot explain differences in malignant potential. © 2008 Wiley‐Liss, Inc.
Intraperitoneal administration of a small interfering RNA targeting nuclear factor‐kappa B with paclitaxel successfully prolongs the survival of xenograft model mice with peritoneal metastasis of gastric cancer
Authors: Inoue Masashi , Matsumoto Sachiko , Saito Hiroaki , Tsujitani Shunichi , Ikeguchi Masahide
Published: September 2008

Activation of nuclear factor‐kappa B (NF‐κB) has been detected in various malignant tumors, including gastric carcinoma, and is associated with tumor growth, metastasis, resistance to chemotherapeutic agents and poor prognosis. Therefore, NF‐κB is a potential target for antitumor therapy. In this study, we used a small interfering RNA (siRNA) to knockdown NF‐κB p65 expression and determined whether intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel was effective for treating peritoneal metastasis of gastric cancer. Western blot analysis revealed that NF‐κB p65 expression was diminished by NF‐κB p65 siRNA. Apoptotic cells were increased after transfection of NF‐κB p65 siRNA compared with control siRNA in the treatment with paclitaxel. In a murine xenograft model, abundant fluorescence was observed on the surface of intraperitoneal nodules of gastric cancer after siRNA administration. Moreover, intraperitoneal administration of NF‐κB p65 siRNA reduced NF‐κB expression in intraperitoneal nodules of gastric cancer. Finally, mice treated by intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel survived for a significantly longer time than mice treated by intraperitoneal administration of paclitaxel alone (p = 0.0002). Taken together, the present results demonstrate that intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel inhibited cancer growth in mice with peritoneal metastasis of gastric cancer. Therefore, intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel may provide a breakthrough in the treatment of peritoneal metastasis of gastric cancer. © 2008 Wiley‐Liss, Inc.
Isosilibinin inhibits advanced human prostate cancer growth in athymic nude mice: Comparison with silymarin and silibinin
Authors: Deep Gagan , Raina Komal , Singh Rana P. , Oberlies Nicholas H. , Kroll David J. , Agarwal Rajesh
Published: September 2008

Earlier studies have shown the cancer chemopreventive efficacy of silymarin and its semi‐purified constituent silibinin against prostate cancer (PCa), but the efficacy of other constituents of silymarin is largely unknown. In the present study, we assessed the in vivo growth inhibitory efficacy of one such constituent isosilibinin (a 50:50 mixture of isosilybin A and isosilybin B) in comparison with silymarin and silibinin in human PCa DU145 xenograft in athymic nude mice. Isosilibinin feeding (200 mg/kg body weight per day) significantly inhibited the growth of xenograft after 53 days of treatment (p ≤ 0.005), which was equally or slightly better effective than silymarin and silibinin, respectively. Treatment with isosilibinin, silymarin and silibinin was stopped after 53 days and tumor volume was measured till 77 days. After 24 days of treatments withdrawal, tumor volume remain decreased, however, it was statistically significant only with isosilibinin (p ≤ 0.05), suggesting its prolonged effect. Biomarker analysis showed that isosilibinin, silymarin and silibinin treatment for 53 days significantly inhibited the immunoreactivity for proliferating cell nuclear antigen (PCNA), microvessel density (CD31) and vascular endothelial growth factor along with significant increase in apoptotic cell population. The PCNA levels in tumors remained significantly low even after 24 days of treatments withdrawal. Western blot analysis of tumor tissue suggested that these flavonolignan formulations differentially alter the expression of cell cycle regulatory molecules, cyclins and Cdks. Overall, the results of present study suggest that isosilibinin has comparatively better efficacy against PCa and should be further analyzed for its clinical utility. © 2008 Wiley‐Liss, Inc.
Heparanase induces VEGF C and facilitates tumor lymphangiogenesis
Authors: Cohen‐Kaplan Victoria , Naroditsky Inna , Zetser Anna , Ilan Neta , Vlodavsky Israel , Doweck Ilana
Published: September 2008

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains, a class of glycosaminoglycans abundantly present in the extracellular matrix and on the cell surface. Heparanase activity is strongly implicated in tumor angiogenesis and metastasis attributed to remodeling of the subepithelial and subendothelial basement membranes. We hypothesized that similar to its proangiogenic capacity, heparanase is also engaged in lymphangiogenesis and utilized the D2‐40 monoclonal antibody to study lymphangiogenesis in tumor specimens obtained from 65 head and neck carcinoma patients. Lymphatic density was analyzed for association with clinical parameters and heparanase staining. We provide evidence that lymphatic vessel density (LVD) correlates with head and neck lymph node metastasis (N‐stage, p = 0.007) and inversely correlates with tumor cell differentiation (p = 0.007). Notably, heparanase staining correlated with LVD (p = 0.04) and, moreover, with VEGF C levels (p = 0.01). We further demonstrate that heparanase overexpression by epidermoid, breast, melanoma and prostate carcinoma cells induces a 3‐ to 5‐fold elevation in VEGF C expression in vitro and facilitates tumor xenograft lymphangiogenesis in vivo, whereas heparanase gene silencing was associated with decreased VEGF C levels. These findings suggest that heparanase plays a unique dual role in tumor metastasis, facilitating tumor cell invasiveness and inducing VEGF C expression, thereby increasing the density of lymphatic vessels that mobilize metastatic cells. © 2008 Wiley‐Liss, Inc.
Tumor microenvironment: Modulation by decorin and related molecules harboring leucine‐rich tandem motifs
Authors: Goldoni Silvia , Iozzo Renato V.
Published: September 2008

Decorin, the prototype member of the small leucine‐rich proteoglycans, resides in the tumor microenvironment and affects the biology of various types of cancer by downregulating the activity of several receptors involved in cell growth and survival. Decorin binds to and modulates the signaling of the epidermal growth factor receptor and other members of the ErbB family of receptor tyrosine kinases. It exerts its antitumor activity by a dual mechanism: via inhibition of these key receptors through their physical downregulation coupled with attenuation of their signaling, and by binding to and sequestering TGFβ. Decorin also modulates the insulin‐like growth factor receptor and the low‐density lipoprotein receptor‐related protein 1, which indirectly affects the TGFβ receptor pathway. When expressed in tumor xenograft‐bearing mice or injected systemically, decorin inhibits both primary tumor growth and metastatic spreading. In this review, we summarize the latest reports on decorin and related molecules that are relevant to cancer and bring forward the idea of decorin as an anticancer therapeutic and possible prognostic marker for patients affected by various types of tumors. We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin. © 2008 Wiley‐Liss, Inc.
The methylenetetrahydrofolate reductase C677T mutation induces cell‐specific changes in genomic DNA methylation and uracil misincorporation: A possible molecular basis for the site‐specific cancer risk modification
Authors: Sohn Kyoung‐Jin , Jang Hyeran , Campan Mihaela , Weisenberger Daniel J. , Dickhout Jeffrey , Wang Yi‐Cheng , Cho Robert C. , Yates Zoe , Lucock Mark , Chiang En‐Pei , Austin Richard C. , Choi Sang‐Woon , Laird Peter W. , Kim Young‐In
Published: September 2008

The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased risk of colon cancer although it may increase the risk of breast cancer. This polymorphism is associated with changes in intracellular folate cofactors, which may affect DNA methylation and synthesis via altered one‐carbon transfer reactions. We investigated the effect of this mutation on DNA methylation and uracil misincorporation and its interaction with exogenous folate in further modulating these biomarkers of one‐carbon transfer reactions in an in vitro model of the MTHFR 677T mutation in HCT116 colon and MDA‐MB‐435 breast adenocarcinoma cells. In HCT116 cells, the MTHFR 677T mutation was associated with significantly increased genomic DNA methylation when folate supply was adequate or high; however, in the setting of folate insufficiency, this mutation was associated with significantly decreased genomic DNA methylation. In contrast, in MDA‐MB‐435 cells, the MTHFR 677T mutation was associated with significantly decreased genomic DNA methylation when folate supply was adequate or high and with no effect when folate supply was low. The MTHFR 677T mutation was associated with a nonsignificant trend toward decreased and increased uracil misincorporation in HCT116 and MDA‐MB‐435 cells, respectively. Our data demonstrate for the first time a functional consequence of changes in intracellular folate cofactors resulting from the MTHFR 677T mutation in cells derived from the target organs of interest, thus providing a plausible cellular mechanism that may partly explain the site‐specific modification of colon and breast cancer risks associated with the MTHFR C677T mutation. © 2008 Wiley‐Liss, Inc.
Induction of the lysosomal apoptosis pathway by inhibitors of the ubiquitin‐proteasome system
Authors: Berndtsson Maria , Beaujouin Melanie , Rickardson Linda , Havelka Aleksandra Mandic , Larsson Rolf , Westman Jacob , Liaudet‐Coopman Emmanuelle , Linder Stig
Published: September 2008

The lysosomal apoptosis pathway is a potentially interesting therapeutic target. Since apoptosis involving the lysosomal pathway has been described to involve cathepsins, we screened a drug library for agents that induce cathepsin‐dependent apoptosis. Using pharmacological inhibitors and siRNA, we identified 2 structurally related agents (NSC687852 and NSC638646) that induced cathepsin D‐dependent caspase‐cleavage activity in human breast cancer cells. Both agents were found to induce the mitochondrial apoptosis pathway. NSC687852 and NSC638646 were found to inhibit the activity of ubiquitin isopeptidases and to induce the accumulation of high‐molecular‐mass ubiquitins in cells. We show that 3 other inhibitors of the proteasome degradation pathway induce lysosomal membrane permeabilization (LMP) and that cathepsin‐D siRNA inhibits apoptosis induced by these agents. We conclude that a screen for cathepsin‐dependent apoptosis‐inducing agents resulted in the identification of ubiquitin isopeptidase inhibitors and that proteasome inhibitors with different mechanisms of action induce LMP and cathepsin D‐dependent apoptosis. © 2008 Wiley‐Liss, Inc.
Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells
Authors: Slominski Andrzej , Zbytek Blazej , Slominski Radomir
Published: September 2008

High mortality rate for metastatic melanoma is related to its resistant to the current methods of therapy. Melanogenesis is a metabolic pathway characteristic for normal and malignant melanocytes that can affect the behavior of melanoma cells or its surrounding environment. Human melanoma cells in which production of melanin pigment is dependent on tyrosine levels in medium were used for experiments. Peripheral blood mononuclear cells were derived from the buffy coats purchased from Lifeblood Biological Services. Cell pigmentation was evaluated macroscopically, and tyrosinase activity was measured spectrophotometrically. Cell proliferation and viability were measured using lactate dehydrogenase release MTT, [3H]‐thymidine incorporation and DNA content analyses, and gene expression was measured by real time RT‐PCR. Pigmented melanoma cells were significantly less sensitive to cyclophosphamide and to killing action of IL‐2‐activated peripheral blood lymphocytes. The inhibition of melanogenesis by either blocking tyrosinase catalytic site or chelating copper ions sensitized melanoma cells towards cytotoxic action of cyclophosphamide, and amplified immunotoxic activities of IL‐2 activated lymphocytes. Exogenous L‐DOPA inhibited lymphocyte proliferation producing the cell cycle arrest in G1/0 and dramatically inhibited the production of IL‐1beta, TNF‐alpha, IL‐6 and IL‐10. Thus, the active melanogenesis could not only impair the cytotoxic action of cyclophosphamid but also has potent immunosuppressive properties. This resistance to a chemotherapeutic agent or immunotoxic activity of lymphocytes could be reverted by the action of tyrosinase inhibitors. Thus, the inhibition of melanogenesis might represent a valid therapeutic target for the management of advanced melanotic melanomas. © 2008 Wiley‐Liss, Inc.
Assessment of the water–salinity crop production function of wheat using experimental data of the Golestan province, Iran
Authors: Kiani A. R. , Abbasi F.
Published: September 2008

Optimisation of agricultural water management in arid and semi‐arid regions requires the availability of water–salinity crop production functions. A two‐year experiment was conducted in the northern Golestan province of Iran to assess the water–salinity production function of wheat. The treatments in the experiment consisted of four levels of irrigation water, i.e. 50 (W1), 75 (W2), 100 (W3) and 125 (W4) % of crop water requirement, and four levels of water salinity, respectively 1.5 (S1), 8.5 (S2), 11.5 (S3) and 14.2 (S4) dS m−1. The plots were arranged in a randomised complete block design with three replications and water quantity as main plot treatment and water quality as subplot treatment. The data were analysed using linear, quadratic, Cobb–Douglas and transcendental functions, complemented with an economic analysis. The results indicate that for the given climate–soil conditions, transcendental functions best predict wheat yield under both water and salinity stress conditions. Yield reduction caused by a unit increase of matric potential is found to be larger than that caused by a unit increase of osmotic potential. The marginal rate of technical substitution indicates that each one of the two factors studied, namely soil salinity and water supply, can be substituted with the other in a wide range in order to achieve equal amount of yield. Copyright © 2008 John Wiley & Sons, Ltd.
Oxidized carbon nanotubes for simultaneous removal of endrin and Cd(Π) from water and their separation from water
Authors: Peng Xianjia , Jia Jianjun , Luan Zhaokun
Published: September 2008

BACKGROUND: Previous investigation has shown that carbon nanotubes (CNTs) are effective for the removal of organic pollutants and oxidized carbon nanotubes (OCNTs) are effective for the removal of heavy metals. In this investigation, OCNTs were used for simultaneous removal of endrin and Cd(Π) from water. Separation of OCNTs from water was also investigated.

RESULTS: The removal efficiencies of endrin and Cd(Π) by OCNTs were 89–97% and 96–100%, respectively. Endrin removal capacity of OCNTs is approximately the same as that of powdered activated carbon (PAC) and as‐prepared CNTs. Cd(Π) removal capacity of OCNTs is much higher than that of PAC and as‐prepared CNTs. OCNTs can be separated efficiently from water using AlCl3.

CONCLUSION: OCNTs are effective for the simultaneous removal of endrin and Cd(Π) and after adsorption, OCNTs can be separated from water by dosing AlCl3. Copyright © 2008 Society of Chemical Industry
Profiles of xylose reductase, xylitol dehydrogenase and xylitol production under different oxygen transfer volumetric coefficient values
Authors: Branco Ricardo F , dos Santos Julio C , Sarrouh Boutros F , Rivaldi Juan D , Pessoa, Jr Adalberto , da Silva Silvio S
Published: September 2008

BACKGROUND: Xylitol is a sugar alcohol (polyalcohol) with many interesting properties for pharmaceutical and food products. It is currently produced by a chemical process, which has some disadvantages such as high energy requirement. Therefore microbiological production of xylitol has been studied as an alternative, but its viability is dependent on optimisation of the fermentation variables. Among these, aeration is fundamental, because xylitol is produced only under adequate oxygen availability. In most experiments with xylitol‐producing yeasts, low oxygen transfer volumetric coefficient (KLa) values are used to maintain microaerobic conditions. However, in the present study the use of relatively high KLa values resulted in high xylitol production. The effect of aeration was also evaluated via the profiles of xylose reductase (XR) and xylitol dehydrogenase (XD) activities during the experiments.

RESULTS: The highest XR specific activity (1.45 ± 0.21 U mgprotein−1) was achieved during the experiment with the lowest KLa value (12 h−1), while the highest XD specific activity (0.19 ± 0.03 U mgprotein−1) was observed with a KLa value of 25 h−1. Xylitol production was enhanced when KLa was increased from 12 to 50 h−1, which resulted in the best condition observed, corresponding to a xylitol volumetric productivity of 1.50 ± 0.08 gxylitol L−1 h−1 and an efficiency of 71 ± 6.0%.

CONCLUSION: The results showed that the enzyme activities during xylitol bioproduction depend greatly on the initial KLa value (oxygen availability). This finding supplies important information for further studies in molecular biology and genetic engineering aimed at improving xylitol bioproduction. Copyright © 2008 Society of Chemical Industry
Differentiation of international terrorism: attack as threat, means, and violence
Authors: Yokota K. , Watanabe K. , Wachi T. , Hoshino M. , Sato A. , Fujita G.
Published: September 2008

This study examined whether international terrorism could be differentiated into different behavioural themes related to the way of using force. The sample consisted of 217 international terrorist organisations that had perpetrated five or more terrorist incidents. A non‐metric multidimensional scaling analysis revealed that all of the terrorist incidents could be assigned to one of three themes reflecting different styles of the use of force: ‘attack as threat’, ‘attack as means’, and ‘attack as violence’. In the current sample, 189 of the terrorist organisations repeated one theme in more than 50% of their series of incidents, suggesting their preference for one of the three themes. Copyright © 2008 John Wiley & Sons, Ltd.
Efficacy of standard deviational ellipses in the application of criminal geographic profiling
Authors: Kent Joshua , Leitner Michael
Published: September 2008

The premise for this study is that the physical and cultural landscape has a deterministic effect on the location and distribution of serial crime. As a consequence, the distribution of linked crime scenes should exhibit a shape and orientation that is consistent with the underlying landscape. Geographic Profiling models that are able to account for these effects will provide more accurate results than those models that do not. Utilizing basic geographic principles of central tendency and spatial diffusion, this research first analyzed the output of circular and elliptical profile models generated for 30 serial burglaries (n = 164) and 67 serial robberies (n = 370) in Baltimore, Maryland between 1994 and 1997. A comparative analysis of the model output reveals that the Standard Deviational Ellipse is significantly (p = 0.000) better able to predict the home location of a serial offender than profiles generated from circles. Next, the relationship between the orientation of elliptical profiles and the mean linear orientation of the corresponding landscape was assessed to reveal a moderate but significant correlation (r = 0.511, p < 0.001). Together, these findings demonstrate that landscape does impact the locations of crime, and is a measurable parameter that can improve the efficacy of geographic profiling. Copyright © 2008 John Wiley & Sons, Ltd.
Assessment Criteria Indicative of Deception (ACID): an integrated system of investigative interviewing and detecting deception
Authors: Colwell Kevin , Hiscock‐Anisman Cheryl K. , Memon Amina , Taylor Laura , Prewett Jessica
Published: September 2008

This study describes the assimilation and validation of Assessment Criteria Indicative of Deception (ACID). ACID is derived from investigative interviewing, Criteria‐Based Content Analysis, Reality Monitoring, and interpersonal deception. Each component has been previously published. Thirty‐eight university undergraduates entered a professor's office and either stole an exam or replaced an exam that had been stolen previously. They were interviewed 1 week later with the Reality Interview, which is deliberately challenging and aims to enhance the detection of deception. Half responded honestly and completely; half distorted their responses to avoid incrimination. Incentives were provided. Honest responses were longer, more detailed, and contained more admissions of potential mistakes. Most importantly, honest respondents benefited from attempts to enhance recall, whereas these same attempts caused deceptive respondents to provide shorter, more repetitive statements. This is a promising technique; 33 of 38 cases were classified accurately. Discussion includes characteristics of deception, process of deception during an investigative interview, hypothetical interview strategies to facilitate the detection of deception, strengths and weaknesses of the study, and areas for future research. Copyright © 2008 John Wiley & Sons, Ltd.
Distance patterns and disposal sites in rural area homicides committed in Finland
Authors: Häkkänen Helinä , Hurme Katri , Liukkonen Markku
Published: September 2008

The present study examined offender characteristics, distance patterns, and the nature of disposal sites in rural area homicides. Pre‐trial investigation files of cases where victims' bodies were found in rural areas in 1994–2005 (n = 46) and forensic psychiatric examination reports of the offenders were content‐analysed. Psychopathy Check List‐Revised was used to assess psychopathy. Investigators of these homicides filled out a questionnaire on the offender's familiarity with the body disposal area, and MapInfo was used to measure offender/victim‐residence‐to‐crime‐to‐body‐disposal‐site distances. Rural area homicides more frequently involved multiple offenders who were significantly younger than offenders in other homicides. Of the victims, 73% were found in woods and 27% in water. Offenders were familiar with disposal sites in over half of the cases. The victim's gender, close relationship with the offender, and the offender's violent crime history were associated with longer homicide‐scene‐to‐body‐disposal‐site distances. The number of inhabitants and offender's violent crime history were related to longer offender‐residence‐to‐body‐disposal‐site distances. Offender's age, intelligence, or psychopathology bore no significant association with the distance patterns. The results can be applied when searching missing persons in homicide investigations and in prioritising suspects in rural area homicides. Copyright © 2008 John Wiley & Sons, Ltd.
Mathematical modeling of appendicular bone growth in glaucous‐winged gulls
Authors: Hayward James L. , Henson Shandelle M. , Banks John C. , Lyn Sheena L.
Published: September 2008

Development of locomotor activity is crucial in tetrapods. In birds, this development leads to different functions for hindlimbs and forelimbs. The emergence of walking and flying as very different complex behavior patterns only weeks after hatching provides an interesting case study in animal development. We measured the diaphyseal lengths and midshaft diameters of three wing bones (humerus, ulna, and carpometacarpus) and three leg bones (femur, tibiotarsus, and tarsometatarsus) of 79 juvenile (ages 0–42 days) and 13 adult glaucous‐winged gulls (Larus glaucescens), a semiprecocial species. From a suite of nine alternative mathematical models, we used information‐theoretic criteria to determine the best model(s) for length and diameter of each bone as a function of age; that is, we determined the model(s) that obtained the best tradeoff between the minimized sum of squared residuals and the number of parameters used to fit the model. The Janoschek and Holling III models best described bone growth, with at least one of these models yielding an R2 ≥ 0.94 for every dimension except tarsometatarsus diameter (R2 = 0.87). We used the best growth models to construct accurate allometric comparisons of the bones. Early maximal absolute growth rates characterize the humerus, femur, and tarsometatarsus, bones that assume adult‐type support functions relatively early during juvenile development. Leg bone lengths exhibit more rapid but less sustained relative growth than wing bone lengths. Wing bone diameters are initially smaller than leg bone diameters, although this relationship is reversed by fledging. Wing bones and the femur approach adult length by fledging but continue to increase in diameter past fledging; the tibiotarsus and tarsometatarsus approach both adult length and diameter by fledging. In short, the pattern of bone growth in this semiprecocial species reflects the changing behavioral needs of the developing organism. J. Morphol., 2009. © 2008 Wiley‐Liss, Inc.