bluuebunny/crossref_metadata_2025 huggingface dataset:
Sand detachment by wind‐driven raindrops
Authors: Erpul G. , Gabriels D. , Norton L. D.
Published: February 2005

Wind movement and velocity can have a profound effect on some aspects of the soil erosion process. In the case of wind‐driven rain, differences in raindrop trajectory are expected: wind‐driven raindrops achieve some degree of horizontal velocity, which increases their resultant impact velocity and they strike the soil surface at an angle deviated from the vertical under the effects of both gravitational and drag forces. However, not much is known about the physical impact of raindrops on a soil in situations where this impact is at an angle, and it is also not precise known if oblique raindrops have stronger erosive effects than vertical ones. A series of tests was conducted to assess the effect of wind velocities on sand detachment from splash cups in a wind tunnel facility equipped with a rainfall simulator. Splash cups packed with standard sand were exposed to windless rains and to rains driven by horizontal wind velocities of 6, 10 and 14 m s−1 to evaluate the sand detachment by wind‐driven raindrops. The average angle of rain inclination from vertical was calculated from the direct intensity measurements implemented with windward and leeward‐facing raingauges placed at different slopes. A kinetic energy sensor measured energy of windless and wind‐driven rains. Results showed that the kinetic energy flux calculated by the resultant impact velocity of drops adequately described the sand detachment from the splash cups by wind‐driven raindrops. However, an additional analysis of Pearson correlation coefficients using the velocity components rather than the resultant velocity of wind‐driven raindrops indicated that the energy flux related to the horizontal component of wind‐driven raindrops had a greater correlation with sand detachment than that related to the normal component. This finding contradicted the general assumption that the component of velocity normal to the surface is related to the detachment. Copyright © 2005 John Wiley & Sons, Ltd.
Rapid assessment of field erosion and sediment transport pathways in cultivated catchments after heavy rainfall events
Authors: van Dijk P. M. , Auzet A.‐V. , Lemmel M.
Published: February 2005

This paper explores a scale‐adapted erosion mapping method which aims at a rapid assessment of field erosion and sediment transport pathways in catchments up to several square kilometres and compares the results with the output of a well‐known erosion model (LISEM). The mapping method is based on an event‐defined classification scheme of erosion intensity (zero, weak, moderate and strong) that is applied to arable fields, in combination with incision measurements of erosion features for each erosion intensity class on a small sample of fields. Sediment deposition is classified on the basis of quantity indicators and abundance. In addition, relevant conditions and erosion factors are determined for each field.

The method was applied to an agricultural catchment (4·2 km2) in the Sundgau (Alsace), after a short but violent thunderstorm in May 2001, to illustrate its potential use and its limitations. The rainfall event led to strong erosion on the arable fields and a muddy flow that caused significant damage in the built‐up area. On the basis of the analyses of the incision measurements in combination with the mapping of erosion intensity classes, total erosion for the catchment was estimated as 15 000 t (an average of about 36 t[sol ]ha). Sediment deposition was found to occur in three major locations: (1) in thalwegs at the interface between maize and downslope winter wheat fields, (2) in downslope headlands where the flow direction suddenly changed due to oriented tillage structures in the perpendicular direction, and (3) the lowest corners of fields which collect all the runoff from the field. Preliminary data analyses suggest that erosion intensity is related to field size and[sol ]or tillage direction and to slope morphology. Model output (LISEM) appeared to depend more strongly on slope gradient than the results obtained with the mapping method.

The method yields a database, which can be used as a foundation for conservation strategies in small regions with similar land use and geomorphology. The mapping and modelling methods are compared, and their complementary aspects are highlighted. Copyright © 2005 John Wiley & Sons, Ltd.
A cytochrome P450 2B6 meditated gene therapy strategy to enhance the effects of radiation or cyclophosphamide when combined with the bioreductive drug AQ4N
Authors: McErlane Verna , Yakkundi Anita , McCarthy Helen O. , Hughes Ciara M. , Patterson Laurence H. , Hirst David G. , Robson Tracy , McKeown Stephanie R.
Published: February 2005

Background

AQ4N is metabolised in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Most solid tumours are known to contain regions of hypoxia whereas levels of CYPs have been found to vary considerably. Enhancement of CYP levels may be obtained using gene‐directed enzyme prodrug therapy (GDEPT). We have therefore examined the potential of a CYP2B6‐mediated GDEPT strategy to enhance the anti‐tumour effect of the combination of AQ4N with radiation or cyclophosphamide (CPA).

Methods

In vitro and in vivo transient transfection of human CYP2B6 ± CYP reductase (CYPRED) was investigated in RIF‐1 mouse tumours. Efficacy in vitro was assessed using the alkaline comet assay (ACA). In vivo, the time to reach 4× the treatment volume (quadrupling time; VQT) was used as the end point.

Results

When CYP2B6 was transfected into RIF‐1 cells and treated with AQ4N under hypoxic conditions there was a significant increase in DNA damage (measured by the ACA) compared with non‐transfected cells. In vivo, a single intra‐tumoural injection of a CYP2B6 vector construct significantly enhanced tumour growth delay in combination with AQ4N (100 mg/kg) and 10 Gy X‐rays. AQ4N (100 mg/kg) and CPA (100 mg/kg) with CYP2B6 and CYPRED also enhanced tumour growth delay; this effect became significant when the schedule was repeated 14 days later (p = 0.0197).

Conclusions

The results show the efficacy of a CYP2B6‐mediated GDEPT strategy for bioreduction of AQ4N; this may offer an additional approach to target radiation‐ and chemo‐resistant hypoxic tumours that should enhance overall tumour control. Copyright © 2005 John Wiley & Sons, Ltd.
A model to predict the residual life of aircraft engines based upon oil analysis data
Authors: Wang Wenbin , Zhang Wenjuan
Published: February 2005

This paper reports on a study using the available oil monitoring information, such as the data obtained using the Spectrometric Oil Analysis Programme (SOAP), to predict the residual life of a set of aircraft engines. The relationship between oil monitoring information and the residual life is established using the concept of the proportional residual, which states that the predicted residual life may be proportional to the wear increment measured by the oil analysis programmes. Assuming such a relationship between wear and the residual life exists, we formulated a recursive prediction model for the item's residual life given measured oil monitoring information to date. A set of censored life data of 30 aircraft engines (right censored due to preventive overhaul) along with the history of their monitored metal concentration information are available to us. The metal concentration information includes many variables, such as Fe, Cu, Al, etc.; not all of them are useful, and some of them may be correlated. The principal component analysis (PCA) has been adopted to reduce the dimension of the original data set and to produce a new set of uncorrelated variables, which we shall use in the prediction model. The procedure associated with estimating model parameters is discussed. The model is fitted to the actual SOAP data from the aircraft engines, and the goodness‐of‐fit test has been carried out. © 2005 Wiley Periodicals, Inc. Naval Research Logistics, 2005.
Benefits from an uncertainty management intervention for African–American and Caucasian older long‐term breast cancer survivors
Authors: Mishel Merle H. , Germino Barbara B. , Gil Karen M. , Belyea Michael , LaNey Iris Carlton , Stewart Janet , Porter Laura , Clayton Margaret
Published: February 2005

In a randomized controlled design, this study tested the efficacy of a theoretically based uncertainty management intervention delivered to older long‐term breast cancer survivors. The sample included 509 recurrence‐free women (360 Caucasian, 149 African–American women) with a mean age of 64 years (S.D.=8.9 years) who were 5–9 years post‐treated for breast cancer. Women were randomly assigned to either the intervention or usual care control condition. The intervention was delivered during four weekly telephone sessions, in which study nurses guided cancer survivors in the use of audiotaped cognitive–behavioral strategies to manage uncertainty about recurrence, and a self‐help manual designed to help women understand and manage long‐term treatment side effects and other symptoms. Treatment outcome data on uncertainty management were gathered at pre‐intervention and 10‐months afterward. Repeated measures MANOVA evaluating treatment group, ethnic group, and treatment by ethnic interaction effects indicated that training in uncertainty management resulted in improvements in cognitive reframing, cancer knowledge, patient–health care provider communication, and a variety of coping skills. Results are discussed in terms of the importance of theory‐based interventions for cancer survivors that target triggers of uncertainty about recurrence and in terms of ethnic differences in response to the intervention. Copyright © 2005 John Wiley & Sons, Ltd.
How to make auxetic fibre reinforced composites
Authors: Alderson K. L. , Simkins V. R. , Coenen V. L. , Davies P. J. , Alderson A. , Evans K. E.
Published: February 2005

Auxetic composite materials can be produced either from conventional components via specially designed configurations or from auxetic components. This paper reviews manufacturing methods for both these scenarios. It then looks at the possibility of property enhancements in both low velocity impact and fibre pull out due to the negative Poisson's ratio. Tests revealed that auxetic carbon fibre composites made from commercially available prepreg show evidence of increased resistance to low velocity impact and static indentation with a smaller area of damage. Also, using auxetic fibres in composite materials is shown to produce a higher resistance to fibre pullout. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Molecular dynamics study of the high‐temperature elasticity of SiO2 polymorphs: Structural phase transition and elastic anomaly
Authors: Kimizuka Hajime , Kaburaki Hideo
Published: February 2005

The elastic properties of cristobalite and quartz, the typical polymorphs of SiO2, are studied with particular emphasis on the structural phase transition and the high‐temperature phase. Using the equilibrium molecular dynamics (MD) method with a stress‐fluctuation formula, we have successfully evaluated the adiabatic elastic constants (Cij) of both cristobalite and quartz in a wide temperature range, including the α–β phase‐transition region. In the results for cristobalite, the anomalous property of a negative Poisson's ratio appears over the entire temperature range of 300–1800 K, where the bulk modulus is extremely low compared with the shear modulus. However, the mechanisms differ between the α‐ and β‐phases, according to the structural data obtained from the MD simulations. On the other hand, quartz exhibits a negative Poisson's ratio in the narrow temperature region between ca. 750 and 825 K before the phase transition occurs. After the transition to the β‐phase, the bulk modulus is shown to increase sharply, and a positive value of Poisson's ratio is recovered. For cristobalite as well as quartz, we have confirmed that the recovery of bulk Cij's in the β‐phase can be attributed to internal relaxations, which arise from the cooperative motions of corner‐linked SiO4 tetrahedra. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Structural changes in amorphous Fe41Ni40Zr7B12 alloy under heat treatment
Authors: Kostyrya S. , Śniadecki Z. , Idzikowski B.
Published: February 2005

The Fe41Ni40Zr7B12 alloy has been obtained by a melt–spinning technique in the glassy state. It revealed a narrow supercooled liquid temperature range ΔTx of about 16 K. The structural behaviour vs. temperature of the alloy has been examined by differential scanning calorimetry (DSC) under continuous heating (in the wide range of heating rates: 10–50 K/s). The enthalpy of crystallization ΔH is about 125 J/g and we have found that the change in ΔH with the heating rate is negligible and does not exceed 10%. Activation energy of crystallization was estimated by Kissinger's method to be about 296 kJ/mol for the first crystallization stage. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Poisson's ratio of degenerate crystalline phases of three‐dimensional hard dimers and hard cyclic trimers
Authors: Kowalik M. , Wojciechowski K. W.
Published: February 2005

Monte Carlo simulations of two three‐dimensional hard‐body models, hard dimers and hard cyclic trimers, were performed in the NpT ensemble. The Poisson's ratio was determined for degenerate crystalline phases in both systems. In contrast to the results of analogous simulations in two‐dimensions, positive values were obtained both for the dimers and the trimers. However, the Poisson's ratio of the trimers was lower than that for the dimers and the latter was lower than that for the spheres. This suggests that a negative Poisson's ratio may be obtained for molecules composed of more spheres. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Expanding the range of auxetic polymeric products using a novel melt‐spinning route
Authors: Ravirala N. , Alderson A. , Alderson K. L. , Davies P. J.
Published: February 2005

The first auxetic fibre was successfully produced in polypropylene using a novel melt‐spinning route. These fibres were extruded at 159 °C with a screw speed 10 rpm (1.05 rad s–1) and 2 mpm (0.03 m s–1) take‐up speed. Characterisation of these fibres involved optical techniques (videoextensometry) to measure the strains along both the length and the width simultaneously during deformation. The unique processing route has now been developed to expand the range of auxetic extruded polymeric products. We report here that auxetic polypropylene films have been developed, and auxetic polyester and polyamide fibres have now been produced. We also report the development of a simple rough particle model to predict auxetic behaviour that may be applicable to the developed fibres and films. Finally, a review of some potential applications for auxetic fibres and films will be presented. These include as reinforcements in composites, anchoring devices, smart bandages for health‐care, breathable packaging and tear resistant films. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Auxetic behaviour: appearance and engineering applications
Authors: Stavroulakis G. E.
Published: February 2005

Materials with negative Poisson's ratio are characterized as auxetic materials. They arise quite rarely in nature, so that our engineering intuition can not help us understand their mechanical behaviour or, further, use them effectively for innovative products and processes. From a literature review and from analytical calculations confirmed with the use of numerical homogenization, it seems that some nonconvex‐shaped (re‐entrant) microstructure is the most understandable origin of the auxetic behaviour. The picture is quite clear in elastostatics, for which a quite large number of potential applications have been discussed in the engineering literature. Analogous problems in elastodynamics and in the area of viscoelasticity have not been discussed thoroughly in the open literature. The purpose of this article is to summarize the available knowledge in the area of auxetics and to point out interesting directions for further research and development work. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stereographic projections of Poisson's ratio in auxetic crystals
Authors: Tokmakova S. P.
Published: February 2005

Auxetic behavior (negative values of Poisson's ratio) in some cubic metals for a stretch along a cube‐face diagonal was investigated in detail by R. H. Baughman et al., F. Milstein, K. Huang, M. Jain, M. P. Verma. Directions with extreme values of Poisson's ratio in crystals for a stretch along a cube‐face diagonal and corresponding lateral strain along the orthogonal cube‐face diagonal and cube‐axis were considered by the authors. In this paper the stereographic projections of Poisson's ratio for a set of natural crystals with cubic, hexagonal and monoclinic symmetry were computed. From these stereographic projections the Poisson's ratio for any possible directions of stretch and lateral strain in the crystal were calculated and orientations of stretch and lateral strain with extreme values of Poisson's ratio were obtained. Crystals with auxetic behavior were revealed. Orientations of stretch directions and lateral strain directions with negative values of Poisson's ratio were determined. By analysis of the above results cuts with optimal negative values of Poisson's ratio were revealed in zinc, molybdenum sulfide, carbon, graphite, polypropylene, monoclinic natural minerals labradorite and augite, a complex silicate and in a set of cubic alloys. The exotic behavior of change of cross‐section of a cylindrical rod during stretching along the rod axis was revealed in the naturally‐occurring mineral SiO2 cristobalite – an example of a molecular auxetic. The elastic constants of crystals from the manual of Landolt–Börnstein were used in the calculations. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Another designer steroid: discovery, synthesis, and detection of ‘madol’ in urine
Authors: Sekera Michael H. , Ahrens Brian D. , Chang Yu‐Chen , Starcevic Borislav , Georgakopoulos Costas , Catlin Don H.
Published: February 2005

Madol (17α‐methyl‐5α‐androst‐2‐en‐17β‐ol) was identified in an oily product received by our laboratory in the context of our investigations of designer steroids. The product allegedly contained an anabolic steroid not screened for in routine sport doping control urine tests. Madol was synthesized by Grignard methylation of 5α‐androst‐2‐en‐17‐one and characterized by mass spectrometry and NMR spectroscopy. We developed a method for rapid screening of urine samples by gas chromatography/mass spectrometry (GC/MS) of trimethylsilylated madol (monitoring m/z 143, 270, and 345). A baboon administration study showed that madol and a metabolite are excreted in urine. In vitro incubation with human liver microsomes yielded the same metabolite. Madol is only the third steroid never commercially marketed to be found in the context of performance‐enhancing drugs in sports. Copyright © 2005 John Wiley & Sons, Ltd.
Evaluation of Blood Flow by Color Doppler Sonography in Free Jejunal Interposition Grafts for Cervical Esophageal Reconstruction
Authors: Ueno Masakatsu , Osugi Harushi , Suehiro Shigefumi , Nishimura Yoshihiko , Takada Nobuyasu , Takemura Masashi , Kinoshita Hiroaki
Published: February 2005

The failure of the vascular anastmoses is a devastating complication in free jejunum transplantation. We used color Doppler sonography to estimate blood flow in free jejunal grafts in 21 patients who underwent radical pharyngoesophagectomy. Fast Fourier transform (FFT) analysis of blood flow, the pulsatility index (PI) as a measure of peripheral vascular resistance, and thickening of the graft wall were evaluated for predictive value. The arterial wave patterns were classified into three types based on systolic–diastolic differences and magnitude of flow. Type I was physiologic flow, type III overtly pathologic, and type II intermediate. The three patients who required vascular reanastomoses intraoperatively had a type II pattern that degenerated to type III within 15 minutes. The PI increased to 3.5 to 4.5 over 1 hour. In the one patient who required retransplantation, the wave pattern became type III by 18 hours and had disappeared by 24 hours, at which point the PI could not be measured. Jejunal thickening increased from 1.0 mm to 5.0 mm after 24 hours, even in healthy grafts. Monitoring blood flow during the 24 hours after surgery is critical. A type III wave pattern or a PI >2.5 is an indication for reexploration. Doppler sonography offers a noninvasive way to measure blood flow in jejunal grafts semiquantitatively and can predict free jejunal graft failure.
Intraoperative Ultrasound‐Guided Excision of Nonpalpable Breast Lesions
Authors: Bennett I. C. , Greenslade J. , Chiam H.
Published: February 2005

The methods commonly used to guide surgical excision of impalpable breast lesions include preoperative placement of hookwires, carbon injections, and, more recently, radioisotope injections. However, all of these techniques have disadvantages, not the least of which is subjecting the patient to an additional stressful and often traumatic procedure preoperatively. The use of intraoperative ultrasound to guide the excision of sonographically visible impalpable lesions is a new technique that avoids the need for a preoperative localization procedure. This report describes one of the author’s (I.B.) personal series of ultrasound‐guided breast excisions, collating data collected prospectively, and reviews the efficacy of this technique. Data in relation to 115 ultrasound guided breast excisions performed in 103 patients were reviewed. The technique of using a high‐frequency real‐time ultrasound probe intraoperatively to localize and guide excision of breast abnormalities is described. There were no failed excisions, as confirmed by specimen sonography, pathology findings, and/or follow‐up ultrasound. Breast malignancies comprised 42% of all excised lesions, and of these, adequate margins of excision were achieved at the first operation in 93% of cases. Direct ultrasound localization of the lesion at the time of surgery allowed optimal placement of the incision and eliminated delays in operating time because specimens did not have to be sent to the Radiology Department for confirmation of excision. Intraoperative ultrasound‐guided excision is a safe and efficient technique in the management of impalpable, sonographically visible breast lesions, and early reports in the world literature support the findings of this series, which show it to have significant advantages over other current methods, particularly with respect to a reduction in patient anxiety and improved surgical resection margins.
Effects of Irradiation Combined with Cis‐diamminedichloroplatinum (CDDP) Suppository in Rabbit VX2 Rectal Tumors
Authors: Wakatsuki Kazuo , Oda Kenji , Koda Keiji , Seike Kazuhiro , Takiguchi Nobuhiro , Saito Norio , Miyazaki Masaru
Published: February 2005

To decrease local recurrence and increase disease free survival, various preoperative therapies for patients with advanced rectal cancer have been studied. Cis‐diamminedichloroplatinum (II) (CDDP) has become one of the most widely used cancer chemotherapeutic drugs. It has also been found to have radiosensitizing properties. In this experimental study, the efficacy of chemoradiotherapy using a novel CDDP suppository, and one with mixed micelles, was examined in a rabbit VX2 rectal tumor model. Rabbits were divided into four groups: control group, irradiation (R) group, CDDP suppository plus irradiation (CR) group, and mixed micelles plus CDDP suppository plus irradiation (CMR) group. Tumor growth ratios were reduced significantly in the CR and CMR groups as compared with the ratio in the control group. Microscopically, response rates of main tumors were 0%, 33.3%, 70.0%, and 91. 7%, respectively. The number of metastatic lymph nodes in the CR and CMR groups decreased significantly compared to the control group and the R group. The microscopic response rates of metastatic lymph nodes were 0%, 11.1%, 40.0%, and 41.7%, respectively. Lung metastases were observed in three rabbits in the R group, and in one rabbit in the CMR group. Tissue platinum concentrations both in tumors and in regional lymph nodes increased significantly when mixed micelles were used. Chemoradiotherapy using the CDDP suppository and mixed micelles was effective for local control in the rabbit VX2 rectal tumor model.
Treatment of Gastrointestinal Stromal Tumors with Imatinib Mesylate:A Major Breakthrough in the Understanding of Tumor‐specific Molecular Characteristics
Authors: de Mestier Philippe , Guetz Gaetan des
Published: February 2005

A specific treatment for gastrointestinal stromal tumors (GIST) has been found through improved understanding of the molecular mechanism of carcinogenesis. GIST are radio and chemo‐resistant (less than 10 objective responses). Stromal tumors originate from the multiplication of the cells of Cajal, which intervene in intestinal motility and express the c‐Kit gene, also called CD117, on their surface. CD117 is a protein with tyrosine kinase activity, and can be demonstrated through immunohistochemical staining techniques.

Treatment with Imatinib mesylate (Glivec), a recently discovered selective inhibitor of tyrosine kinases already used in chronic myeloid leukemia (in which an overexpression of tyrosine kinase is observed) was associated with tumor regression of more than 50% in the initial series of patients with GIST treated in 2001. Since then, approximately 2,000 patients have been included in therapeutic trials, with an objective response rate between 60% and 70% 12 to 18 months after inclusion. The clinical benefit has been estimated at 80% to 90% in patients whose chance of survival until now has been less than 30% at one year (median survival 18 months). Nonetheless, imatinib mesylate has not shown any activity in CD117‐negative sarcoma (10% of sarcoma). The therapeutic importance of this drug in the treatment of solid GI tumors deemed inoperable is considerable.
Hepatic Tumor Growth: Target for Angiogenesis Inhibition?
Authors: Sarraf‐Yazdi Shiva , Mi Jing , Clary Bryan M.
Published: February 2005

Pathologic angiogenesis induced by a tumor is essential for its survival. The promise of tumor inhibition by targeting angiogenesis over the past several years has translated into numerous ongoing clinical trials. Recently, in a phase III trial involving patients with metastatic colorectal cancer, Bevacizumab (Genentech, Inc, San Francisco, CA), a recombinant humanized monoclonal antibody against vascular endothelial growth factor used in conjunction with standard chemotherapy was shown to increase survival, progression‐free survival, response rate, and duration of response compared to chemotherapy alone. Thus far, duration of the increased response remains less than 6 months. The majority of deaths in patients with colorectal cancer are related to hepatic metastases. It is hoped that novel approaches directed at the complex interactions between tumor and microenvironment in the angiogenic process will strengthen the therapeutic armamentarium against hepatic malignancies.
Roles of Thymosins in Cancers and Other Organ Systems
Authors: Chen Changyi , Li Min , Yang Hui , Chai Hong , Fisher William , Yao Qizhi
Published: February 2005

Thymosins are small peptides, originally identified from the thymus, but now known to be more widely distributed in many tissues and cells. Thymosins are divided into three main groups, α‐, β‐, and γ‐thymosins, based on their isoelectric points. α‐thymosins (ProTα, Tαl) have nuclear localization and are involved in transcription and/or DNA replications; whereas β‐thymosins (Tβ4, Tβ10, Tβl5) have cytoplasmic localization and show high affinity to G‐actin for cell mobility. Furthermore, it is well known that both α‐ and β‐thymosins play important roles in modulating immune response, vascular biology, and cancer pathogenesis. More importantly, thymosins may have significant clinical applications. They may serve as molecular markers for the diagnosis and prognosis of certain diseases. In addition, they could be molecular targets of certain diseases or be used as therapeutic agents to treat certain diseases. However, the molecular mechanisms of action of thymosins are largely unknown. This review not only presents recent advances of basic science research of thymosins and their clinical applications but provides thoughtful views for future directions of investigation on thymosins.
Gene Profiling of High Risk Neuroblastoma
Authors: Vasudevan Sanjeev A. , Nuchtern Jed G.
Published: February 2005

Neuroblastoma, a cancer of young children, is well known for its diverse pattern of presentation. Approximately one‐half of children have localized tumors that can be cured with surgery alone. The remaining children have widespread metastatic disease or quite large, aggressive, localized tumors. These children have a poor long‐term survival rate of approximately 30%. We review the prognostically significant histologic and molecular features of high risk neuroblastoma and propose an algorithm to dissect further the differentially expressed genes that define the phenotype of this disease. Over the past 25 years, much effort has gone into establishing reliable prognostic indicators of high risk disease. For neuroblastoma, age, stage, and histopathology have time and again correlated well with outcomes. Chromosomal number, or ploidy, and amplification of the MYCN oncogene have proved to be equally as important and are commonly used to stratify patient risk. Other potentially lucrative markers include chromosome 1p deletion, chromosome 17q gain, receptor tyrosine kinases A and B (trk‐A, trk‐B), CD44, CXCR4, and multidrug resistance associated protein (MRP). With the onset of new technology, expression microarrays are now being used to profile advanced‐stage neuroblastoma on a larger scale. Genes particular to cell cycle control, DNA/RNA replication, ribosomal synthesis, neuronal differentiation, and intracellular/extracellular signal transduction have been identified through differential expression analysis. We present our research on the MYCN transcription factor and target gene, MCM7, to show the utility of this approach.
Intravenous Delivery of Liposome‐mediated Nonviral DNA Is Less Toxic than Intraperitoneal Delivery in Mice
Authors: Wang X. P. , Yazawa K. , Templeton N. S. , Yang J. , Liu Shihe , Li Zhijun , Li M. , Yao Q. , Chen C. , Brunicardi F. C.
Published: February 2005

Suicide gene therapy has been shown to be an effective means of destroying pancreatic cancer cells. Liposomes have been described as having better efficacy in gene delivery, and an advantage of using liposomes as gene carriers is that they can be used repeatedly in vivo. The objective of this study is to compare the effect of gene delivery routes and to determine whether systemic delivery of the rat insulin promoter (RIP)–directed suicide gene construct would permit cell‐specific gene delivery in vivo. Severe combined immunodeficient (SCID) mice were injected with liposome‐RIP‐TK (thymidine kinase) complex by either the intraperitoneal or the intravenous route. Twenty‐four hours post gene delivery, mice received ganciclovir (GCV) treatment twice daily for 14 days. Mice were sacrificed at various time points. Complete necropsy and serum chemistry analysis were performed. Islet morphology was determined using hematoxylin and eosin (H&E) staining. Serum glucose and insulin levels were also determined. To determine the toxic effect on pancreatic islet cells, immunostaining of insulin‐producing and glucagon‐producing cells was carried out at each time point. H&E staining indicated that both intravenous and intraperitoneal liposome‐RIP‐TK gene expression had no effect in normal endocrine islet cells. Both gene‐delivery routes in mice resulted in normal glycemia and serum insulin levels. The endocrine islets were intact, with a normal distribution pattern of insulin‐producing beta cells and glucagon‐secreting alpha cells. However, serum chemistry analysis revealed significantly elevated levels of liver enzymes; suggesting that possible liver damage had occurred with the intraperitoneal gene delivery of liposome‐pRIP‐TK. Intravenous liposome‐mediated gene delivery had no effect on liver enzyme levels. Liposome‐mediated gene delivery via intravenous injection was less toxic than intraperitoneal delivery. This gene‐delivery route requires fewer liposome‐DNA complexes and maintains normal liver function. Thus, intravenous delivery of gene therapy would be superior to intraperitoneal administration of gene therapy in mice.
Tissue MicroArray Analyses of Pancreatic Duodenal Homeobox‐1 in Human Cancers
Authors: Wang Xiao‐Ping , Li Zhi‐Jun , Magnusson Jonas , Brunicardi F. Charles
Published: February 2005

In previous studies, we demonstrated that rat insulin promoter (RIP)‐driven gene therapy successfully targeted human pancreatic tumor PANC‐1 cells and mouse insulinoma NIT‐1 cells, which are both pancreatic duodenal homeobox‐1 (PDX‐1)‐positive. The purpose of this study was to perform a human tissue array analysis to determine potential targets for RIP‐driven gene therapy. A custom‐designed tissue MicroArray analysis of various human cancer specimens was performed using a PDX‐1 polyclonal antibody generated in our laboratory. The custom‐designed Tissue MicroArray of human tumor specimens consists of human cancer specimens from different origins, such as the pancreas, breast, colon, prostate, kidney, liver, lung, and ovary. A panel of normal human specimens from 20 organs or tissues was used as a control. All tissues were fixed in formalin and embedded in paraffin. The immunohistochemistry studies of the cytoplasm and the nuclear expression levels were compared using the Loda method and blind reviews. Data are presented as the mean ± SEM (p < 0.05 was considered significant by the unpaired student t‐test). PDX‐1 expression intensity was elevated in both benign and malignant tissues from the same patient with pancreas, breast, colon, prostate, and kidney cancers, whereas normal human tissues from control subjects without cancer did not express PDX‐1. These results suggest that PDX‐1 is an early marker for these cancers and could be potentially used as a diagnostic parameter and perhaps could be targeted by PDX‐1‐activated gene therapies, such as RIP‐TK.
Prevention of intracellular oxidation in yeast: the role of vitamin E analogue, Trolox (6‐hydroxy‐2,5,7,8‐tetramethylkroman‐2‐carboxyl acid)
Authors: Raspor P. , Plesničar S. , Gazdag Z. , Pesti M. , Miklavčič M. , Lah B. , Logar‐Marinsek R. , Poljšak B.
Published: February 2005

Reactive oxygen species (ROS) are not only generated in conditions of cellular stress but are also constitutively produced in most cell types by specific metabolic processes. This research focused on a potential antioxidant Trolox (model compound for α‐tocopherol), with the aim to establish exact mechanisms of Trolox intracellular oxidation prevention on model organism Saccharomyces cerevisiae. Measuring intracellular oxidation of Trolox‐treated yeast cells revealed that Trolox decreased intracellular oxidation during normal metabolism. Trolox treatment decreased cyto‐ and geno‐toxicity of treated yeast cells in MES buffer, lowered intracellular oxidation, decreased intracellular peroxides formation, and increased H2O2 degradation and superoxide quenching yeast extract ability.

This study suggests that Trolox treatment provides prevention against intracellular ROS formation. Trolox application as therapeutic agent against intracellular ROS formation would be worth considering. Additionally, results indicate that yeasts are good model organisms for studying intracellular oxidation and oxidative stress. The obtained results on yeast cells might be useful to direct further human‐related search for the Trolox evaluation as a human supplement used for protecting cells against intracellular free radical formation.
Variation and evolution of biomolecular systems: Searching for functional relevance
Authors: Huynen Martijn A. , Gabaldón Toni , Snel Berend
Published: February 2005

The availability of genome sequences and functional genomics data from multiple species enables us to compare the composition of biomolecular systems like biochemical pathways and protein complexes between species. Here, we review small‐ and large‐scale, “genomics‐based” approaches to biomolecular systems variation. In general, caution is required when comparing the results of bioinformatics analyses of genomes or of functional genomics data between species. Limitations to the sensitivity of sequence analysis tools and the noisy nature of genomics data tend to lead to systematic overestimates of the amount of variation. Nevertheless, the results from detailed manual analyses, and of large‐scale analyses that filter out systematic biases, point to a large amount of variation in the composition of biomolecular systems. Such observations challenge our understanding of the function of the systems and their individual components and can potentially facilitate the identification and functional characterization of sub‐systems within a system. Mapping the inter‐species variation of complex biomolecular systems on a phylogenetic species tree allows one to reconstruct their evolution.
Cod recruitment is strongly affected by climate when stock biomass is low
Authors: Brander Keith M.
Published: February 2005

Stocks of Atlantic cod (Gadus morhua) have been declining over much of the North Atlantic for the past 30 years, owing to a combination of overfishing and adverse changes in their environment. In a previous study, environmental effects were introduced as an extra parameter in the stock-recruit relationship, where they act as a multiplier, independent of the level of spawning-stock biomass (SSB). Using a non-parametric pooled analysis of all cod stocks on the European Shelf south of 62°N, it is shown here that environmental variability (as represented by the North Atlantic Oscillation) only has a significant effect on recruitment when the spawning stock is low. This has implications for fisheries management strategies, and for rates of stock recovery, which will be very dependent on environmental conditions.
Ecological indicators based on fish biomass distribution along trophic levels: an application to the Terminos coastal lagoon, Mexico
Authors: Sosa-López Atahualpa , Mouillot David , Do Chi Thang , Ramos-Miranda Julia
Published: February 2005

Cumulative relative biomass trophic level spectra (BTLS) are constructed for the fish community of a tropical coastal lagoon in Mexico to analyse spatio-temporal patterns as a potential ecosystem indicator of multifactor impacts. Data were based on monthly trawl surveys over a single year carried out eighteen years apart. The spectra show significant differences between the two periods, indicating major shifts in the trophic structure of the system. Specifically, biomass of the omnivorous, estuarine species in the middle of the foodweb (originally dominating) has been replaced by carnivorous and herbivorous–detritivorous species. As a consequence, the initial sigmoid shape of the BTLS has tended to become more linear. However, interpretation of the causes involved remains unclear. It is suggested that this potential indicator of trophic status of the fish community reflects a combination of interacting driving forces acting simultaneously in the lagoon: (i) increased marine conditions as well as artificial reefs constructed in adjacent zones may enhance biomass of marine predators and detritivorous species; (ii) attenuation of estuarine influences may lead to decreasing biomass of estuarine generalist species; and (iii) the establishment of a marine protected area may increase predator biomass, causing a decline in prey biomass.
Possible ecosystem impacts of applying MSY policies from single-species assessment
Authors: Walters Carl J. , Christensen Villy , Martell Steven J. , Kitchell James F.
Published: February 2005

Ecosim models have been fitted to time-series data for a wide variety of ecosystems for which there are long-term data that confirm the models' ability to reproduce past responses of many species to harvesting. We subject these model ecosystems to a variety of harvest policies, including options based on harvesting each species at its maximum sustainable yield (MSY) fishing rate. We show that widespread application of single-species MSY policies would in general cause severe deterioration in ecosystem structure, in particular the loss of top predator species. This supports the long-established practice in fisheries management of protecting at least some smaller “forage” species specifically for their value in supporting larger piscivores.
The recruitment of gill-infesting copepods as a categorical predictor of size-at-age data in squid populations
Authors: Pascual S. , González A.F. , Guerra A.
Published: February 2005

The independent effects of host age and size on the recruitment of the gill-infesting copepod parasite Pennella sp. were examined in the short-finned squid (Illex coindetii) from Galician waters (ICES Areas VIIIc–IXa). Older and larger squid had larger parasite infrapopulations, but in general the age of squid described the parasite recruitment to the host population better than did mantle length or body weight of squid. Parasite infrapopulations were markedly clumped or overdispersed in those squid hatchling groups with greater parasite recruitment, indicating close adjustment of host/parasite life cycles. Moreover, the gill infestation did moderate the relationship between age and body weight of squid, though the strength or importance of the variation associated with the relationships is not known. The results show that infestation by pennellids contributes to the variability in squid growth, being one of the multiple categorical predictors of size-at-age data in several infested cephalopod species commercially exploited in European waters.
Closed‐loop supply chains in process industries: An empirical study of producer re‐use issues
Authors: French Monique L. , LaForge R. Lawrence
Published: February 2005

Closed‐loop supply chain research has primarily focused on discrete industries, leaving important issues involving waste disposal and re‐use in process industries unaddressed. This exploratory study investigates re‐use issues and practices related to process industry firms—from the producer's perspective—with the objective of identifying important issues that need further research in the field. Site visits were conducted to identify and clarify re‐use issues unique to process industry firms for the purpose of developing a mail survey instrument. The mail survey provided detailed information about the sources of returned product and materials and the subsequent re‐use decisions made by 141 different manufacturing facilities in a wide variety of process industries including chemicals, food, rubber, and plastics. Results indicate that process industry firms are quite diverse, that some common beliefs about re‐use in process industry firms do not apply to all process types in these industries, and that research efforts are needed in the areas of network design and product acquisition; inventory; production planning and control; and scheduling. The paper concludes by identifying specific research questions important to re‐use in process industry environments.
Long‐term changes in the mesosphere calculated by a two‐dimensional model
Authors: Gruzdev Aleksandr N. , Brasseur Guy P.
Published: February 2005

We have used the interactive two‐dimensional model SOCRATES to investigate the thermal and the chemical response of the mesosphere to the changes in greenhouse gas concentrations observed in the past 50 years (CO2, CH4, water vapor, N2O, CFCs), and to specified changes in gravity wave drag and diffusion in the upper mesosphere. When considering the observed increase in the abundances of greenhouse gases for the past 50 years, a cooling of 3–7 K is calculated in the mesopause region together with a cooling of 4–6 K in the middle mesosphere. Changes in the meridional circulation of the mesosphere damp the pure radiative thermal effect of the greenhouse gases. The largest cooling in the winter upper mesosphere‐mesopause region occurs when the observed increase in concentrations of greenhouse gases and the strengthening of the gravity wave drag and diffusion are considered simultaneously. Depending on the adopted strengthening of the gravity wave drag and diffusion, a cooling varying from typically 6–10 K to 10–20 K over the past 50 years is predicted in the extratropical upper mesosphere during wintertime. In summer, however, consistently with observations, the thermal response calculated by the model is insignificant in the vicinity of the mesopause. Although the calculated cooling of the winter mesopause is still less than suggested by some observations, these results lead to the conclusion that the increase in the abundances of greenhouse gases alone may not entirely explain the observed temperature trends in the mesosphere. Long‐term changes in the dynamics of the middle atmosphere (and the troposphere), including changes in gravity wave activity may have contributed significantly to the observed long‐term changes in thermal structure and chemical composition of the mesosphere.
Backward probability model using multiple observations of contamination to identify groundwater contamination sources at the Massachusetts Military Reservation
Authors: Neupauer R. M. , Wilson J. L.
Published: February 2005

Backward location and travel time probability density functions characterize the possible former locations (or the source location) of contamination that is observed in an aquifer. For an observed contaminant particle the backward location probability density function (PDF) describes its position at a fixed time prior to sampling, and the backward travel time probability density function describes the amount of time required for the particle to travel to the sampling location from a fixed upgradient position. The backward probability model has been developed for a single observation of contamination (e.g., Neupauer and Wilson, 1999). In practical situations, contamination is sampled at multiple locations and times, and these additional data provide information that can be used to better characterize the former position of contamination. Through Bayes' theorem we combine the individual PDFs for each observation to obtain a PDF for multiple observations that describes the possible source locations or release times of all observed contaminant particles, assuming they originated from the same instantaneous point source. We show that the multiple‐observation probability density function is the normalized product of the single‐observation PDFs. The additional information available from multiple observations reduces the variances of the source location and travel time probability density functions and improves the characterization of the contamination source. We apply the backward probability model to a trichloroethylene (TCE) plume at the Massachusetts Military Reservation (MMR). We use four TCE samples distributed throughout the plume to obtain single‐observation and multiple‐observation location and travel time PDFs in three dimensions. These PDFs provide information about the possible sources of contamination. Under assumptions that the existing MMR model is properly calibrated and the conceptual model is correct the results confirm the two suspected sources of contamination and reveal that one or more additional sources is likely.