bluuebunny/crossref_metadata_2025 huggingface dataset:
MANAGEMENT CONTROL SYSTEMSAND STAKEHOLDERS’ INTERESTS IN LITHUANIAN MULTINATIONAL COMPANIES: CASES FROM THE TELECOMMUNICATIONS INDUSTRY
Authors: Jurkštienė Aušra , Darškuvienė Valdonė , Dūda Arūnas
Published: December 2008

The paper addresses the issue of introduction and effectiveness of modern management control systems (MCS) in Lithuanian enterprises controlled by foreign owners. Modern management control systems are supposed to provide local management with useful information, reflecting firm's performance from different stakeholders’ perspectives. However, the tools of management control sometimes fail in providing with this main function. Thus, the question is raised as to the extent to which performance management systems (PMS) are effective within Lithuanian telecommunication companies, when they are implemented by foreign parent companies in the rapidly changing environment of the industry.

The paper reports the findings of a survey of 78 top and middle level managers of two telecommunication companies. Results of the research indicate that differences in the effectiveness of MCS do exist due to the specifics of governance structures within the telecommunication companies. Nevertheless, it is concluded that, when used interactively, a PMS is potentially effective even if a company operates in a rapidly changing environment.
A MATHEMATICAL MODEL OF SELECTING TRANSPORT FACILITIES FOR MULTIMODAL FREIGHT TRANSPORTATION
Authors: Lingaitienė Olga
Published: December 2008

A system of functional relationships between speed, traffic safety and costs, based on a set of criteria describing transportation quality is presented. The overall technological costs of transportation can be determined, when the costs of using road, rail and sea transport are calculated. For this purpose, a case study of creating a mathematical model for choosing the optimal route, taking into account time, costs and safety of transportation, is considered. The model evaluates the time of freight loading and storage at terminals. The total time of transportation, loading and storage differs for particular routes, depending on route structure and terminal operation. Freight safety is calculated in terms of insurance payments, depending on the type of goods, route and time of transportation. The model may be used for calculating any route, when applying the data on particular parks of vehicles.
AGILE FORECASTING OF DYNAMIC LOGISTICS DEMAND
Authors: Miao Xin , Xi Bao
Published: December 2008

The objective of this paper is to study the quantitative forecasting method for agile forecasting of logistics demand in dynamic supply chain environment. Characteristics of dynamic logistics demand and relative forecasting methods are analyzed. In order to enhance the forecasting efficiency and precision, extended Kalman Filter is applied to training artificial neural network, which serves as the agile forecasting algorithm. Some dynamic influencing factors are taken into consideration and further quantified in agile forecasting. Swarm simulation is used to demonstrate the forecasting results. Comparison analysis shows that the forecasting method has better reliability for agile forecasting of dynamic logistics demand.
INVESTIGATING THE DYNAMICS OF PASSENGER ROLLING STOCK DETERIORATION
Authors: Vaičiūnas Gediminas , Lingaitis Leonas Povilas
Published: December 2008

One of the major economic criteria is associated with the growth of maintenance costs of old rail vehicles. The research aims to determine the ageing criteria of passenger rolling stock, which could take into account fuel, diesel oil and repair costs. Therefore, economic criteria based on the above costs are generated and their comparative analysis is made. The research object is Vilnius locomotive depot.
ESTIMATION OF THE NEED FOR HARMONIZATION OF TECHNICAL DEMANDS FOR VEHICLES USED IN TRANSIT COUNTRIES TO DECREASE THREATS MADE BY THE ACCIDENTS, PRESENTED IN THE SELECTED EXAMPLES
Authors: Olejnik Krzysztof
Published: December 2008

The paper shows the need to make harmonization of the technical demands concerning the vehicles used in the traffic. The vehicles moving now on the roads in the transit countries were allowed to be driven according to demands which were milder than the present binding ones. Some rules were changed because the performing technical progress and development of the devices allowed sharpening the demands for the new registered vehicles in order to decrease the number of accidents. It results from the fact that earlier registered vehicles are more susceptible to accidents. The analysis of this problem was presented in 4 selected cases connected with the safety of participants in the traffic. The paper also discusses the need to equip the trucks already used in Poland with the devices of indirect visibility which enable to observe a much bigger area in the neighbourhood of the vehicle. Increase of indirect visibility from the driver's seat improves the safety system of the participants in the road traffic. Application of the demands of the Directive 2003/97 (which is obligatory for the newly produced vehicles) to the vehicles earlier registered can be done by replacement and installment of the new mirrors which contain the bigger areas. The solution to the problem of the limited visibility at the inclined crossing of roads and enlarged crossing by turn to the left is proposed.
CHOSEN ASPECTS OF MUNICIPAL TRANSPORT OPERATION ON THE EXAMPLE OF THE CITY OF LUBLIN
Authors: Niewczas Andrzej , Koszalka Grzegorz , Wrona Jan , Pieniak Daniel
Published: December 2008

The paper presents some aspects of operation of municipal transport system in the city of Lublin (Poland). Organization of Lublin Municipal Transport Company was described, its efficiency and perspectives of development. Particular attention was paid to the rules of adjustment to the EU requirements, and to the influence of demographic and social factors. Infrastructure of public transport in Lublin was analyzed (busses, trolley‐busses, bus stations, fixed objects and bus stops), as well as configuration of bus and trolley‐bus lines. Some specific proposals were also put forward regarding development solutions: development plan of trolley‐bus traction, plan of inter‐connection bus station, development plan of bus traction, introduction of advanced IT solutions into the public transport management and natural gas (CNG) fuelling of the city busses. Keywords: urban transport, urban transport problems.
Multiple sodium channel isoforms and mitogen‐activated protein kinases are present in painful human neuromas
Authors: Black Joel A. , Nikolajsen Lone , Kroner Karsten , Jensen Troels S. , Waxman Stephen G.
Published: December 2008

Objective

Although axons within neuromas have been shown to produce inappropriate spontaneous ectopic discharges, the molecular basis for pain in patients with neuromas is still not fully understood. Because sodium channels are known to play critical roles in neuronal electrogenesis and hyperexcitability, we examined the expression of all the neuronal voltage‐gated sodium channels (Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) within human painful neuromas. We also examined the expression of two mitogen‐activated protein (MAP) kinases, activated p38 and extracellular signal‐regulated kinases 1 and 2 (ERK1/2), which are known to contribute to chronic pain, within these human neuromas.

Methods

We used immunocytochemical methods with specific antibodies to sodium channels Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9, and to activated MAP kinases p38 and ERK1/2 to study by confocal microscopy control and painful neuroma tissue from five patients with well‐documented pain.

Results

We demonstrate upregulation of sodium channel Nav1.3, as well as Nav1.7 and Nav1.8, in blind‐ending axons within human painful neuromas. We also demonstrate upregulation of activated p38 and ERK1/2 MAP kinases in axons within these neuromas.

Interpretation

These results demonstrate that multiple sodium channel isoforms (Nav1.3, Nav1.7, and Nav1.8), as well as activated p38 and ERK1/2 MAP kinases, are expressed in painful human neuromas, indicating that these molecules merit study as possible therapeutic targets for the treatment of pain associated with traumatic neuromas. Ann Neurol 2008;64:644–653
Epigenetics and the nervous system
Authors: Mehler Mark F.
Published: December 2008

We are in the midst of a revolution in the genomic sciences that will forever change the way we view biology and medicine, particularly with respect to brain form, function, development, evolution, plasticity, neurological disease pathogenesis and neural regenerative potential. The application of epigenetic principles has already begun to identify and characterize previously unrecognized molecular signatures of disease latency, onset and progression, mechanisms underlying disease pathogenesis, and responses to new and evolving therapeutic modalities. Moreover, epigenomic medicine promises to usher in a new era of neurological therapeutics designed to promote disease prevention and recovery of seemingly lost neurological function via reprogramming of stem cells, redirecting cell fate decisions and dynamically modulating neural network plasticity and connectivity. Ann Neurol 2008;64:602–617
Modelling and forecasting vehicle stocks using the trends of stochastic Gompertz diffusion models: The case of Spain
Authors: Gutiérrez R. , Gutiérrez‐Sánchez R. , Nafidi A.
Published: December 2008

In the present study, we treat the stochastic homogeneous Gompertz diffusion process (SHGDP) by the approach of the Kolmogorov equation. Firstly, using a transformation in diffusion processes, we show that the probability transition density function of this process has a lognormal time‐dependent distribution, from which the trend and conditional trend functions and the stationary distribution are obtained. Second, the maximum likelihood approach is adapted to the problem of parameters estimation in the drift and the diffusion coefficient using discrete sampling of the process, then the approximated asymptotic confidence intervals of the parameter are obtained. Later, we obtain the corresponding inference of the stochastic homogeneous lognormal diffusion process as limit from the inference of SHGDP when the deceleration factor tends to zero. A statistical methodology, based on the above results, is proposed for trend analysis. Such a methodology is applied to modelling and forecasting vehicle stocks. Finally, an application is given to illustrate the methodology presented using real data, concretely the total vehicle stocks in Spain. Copyright © 2008 John Wiley & Sons, Ltd.
Impact on regional recurrence and survival of axillary surgery in women with node-negative primary breast cancer
Authors: Axelsson C K , Düring M , Christiansen P M , Wamberg P A , Søe K L , Møller S
Published: December 2008

Background

This study examined whether axillary lymph node dissection (ALND) with removal of many normal lymph nodes resulted in a reduced rate of axillary recurrence and better survival, as reported in recent studies.

Methods

The follow-up analyses were based on 8657 patients with node-negative primary breast cancer treated solely by surgery. Median follow-up was 9 years.

Results

The number of lymph nodes removed correlated with a reduction in the rate of subsequent axillary recurrence (from 2·1 to 0·4 per cent; P = 0·037), local recurrence (from 7·4 to 3·8 per cent; P < 0·001) distant metastases (from 15·0 to 10·3 per cent; P < 0·001) and death as first event (from 7·5 to 5·5 per cent; P = 0·012).

Conclusion

When ALND is indicated, at least ten axillary lymph nodes should be retrieved. The role of ALND as primary treatment has decreased significantly during the past decade. The findings leave the concept of the sentinel node biopsy intact, as a highly specific procedure compared to ALND.
Randomized clinical trial comparing decellularized bovine ureter with expanded polytetrafluoroethylene for vascular access
Authors: Chemla E S , Morsy M
Published: December 2008

Background

The SynerGraft® model 100 (SG 100) is a decellularized bovine uereter graft developed to improve on prosthetic conduits for vascular access. Its clinical performance was compared with polytetrafluoroethylene (ePTFE) in a prospective, pilot randomized study.

Methods

Patients requiring haemodialysis with no native vein options were included. Between June 2004 and June 2007, 29 patients received SG 100 and 27 ePTFE grafts. Forty-five patients had undergone previous access surgery. All grafts were between the brachial artery and the axillary vein.

Results

Clinical details were similar between the groups; overall mean(s.d.) follow-up was 469(398) days. After 1 year, there were no significant differences in primary patency (28 per cent for SG 100 versus 48 per cent for ePTFE; P = 0·290), assisted primary patency (52 versus 64 per cent; P = 0·430) or secondary patency (57 versus 68 per cent; P = 0·370). Freedom from infection at 1 year was 96 per cent for SG 100 and 91 per cent for ePTFE (P = 0·410). Fifty-seven further procedures (18 endovascular and 39 surgical) were needed to maintain patency in 50 grafts (23 SG 100 and 27 ePTFE).

Conclusion

Both grafts were adequate conduits for haemodialysis and were amenable to repair. Anticipated advantages for SG 100 were not seen in either patency or stability.
Assessing the affective feelings of two‐ and three‐dimensional objects
Authors: Lee Wen‐Yuan , Luo M. Ronnier , Ou Li‐Chen
Published: December 2008

The aim of this study is to investigate the impact of physical appearance attributes (in terms of color and shape) on our affective feelings of 2D and 3D objects. Twelve colors were studied, each consisting of 12 two‐dimensional and 12 three‐dimensional shapes. This resulted in 144 2D and 144 3D color‐shape combinations. Each color‐shape combination was assessed using 20 emotion scales in a viewing cabinet by a panel of observers with normal color vision. The results show that there are five underlying factors of these 20 scales, i.e., “activity,” “weight,” “heat,” “softness,” and “complexity”. The first three factors were mainly related to color and the other two were linked with shape. © 2008 Wiley Periodicals, Inc. Col Res Appl, 34, 75–83, 2009.
The nature of complex organizations: The case of Cooperative Extension
Authors: Franz Nancy K. , Townson Lisa
Published: December 2008

The authors provide an overview of the Cooperative Extension System and its program evaluation challenges. Part of the historic land‐grant system, Extension exists in all states and territories of the United States and is funded through federal, state, and local (usually county) appropriations, as well as competitive grants and other sources. Complex funding, staffing, and accountability structures combined with widely varying programs and delivery methods make program development and evaluation challenging for Extension. Although each state's Extension service operates autonomously, they all share a need to communicate program impacts and public value, which has become the main driver for program evaluation. Further, organizational factors such as variation in program evaluation support across states, widely varied evaluation cultures, and the grassroots nature of including stakeholders in program development add even more complexity to evaluating Extension programs. © Wiley Periodicals, Inc.
Evaluating multilevel programs
Authors: King Nicelma J. , Cooksy Leslie J.
Published: December 2008

Multilevel programs—that is, programs with multiple levels of administration, funding, and implementation—present dynamic and challenging environments for the conduct and use of evaluation. The challenges include questions, priorities, audiences, and purposes that vary at each level. This chapter discusses the challenges as well as the opportunities for increasing the value of evaluation at the federal, state, and local levels. Five areas of information are used as a framework for the discussion: (1) Who came? (2) Who cares? (3) What was the intervention? (4) What changed, and what difference did it make? (5) How much did it cost? Using the Cooperative Extension System and other cases as illustrations, the authors describe the relative emphases given to these questions at the different levels, the motivations for those emphases, and the opportunities evaluators can take to make multilevel evaluations useful to audiences at all levels. © Wiley Periodicals, Inc.
Organizational structures that support internal program evaluation
Authors: Lambur Michael T.
Published: December 2008

This chapter explores how the structure of large complex organizations such as Cooperative Extension affects their ability to support internal evaluation of their programs and activities. Following a literature review of organizational structure and its relation to internal evaluation capacity, the chapter presents the results of interviews with 10 selected Extension evaluators. Four structures for evaluation in Extension organizations are identified: (1) a separate evaluation unit, (2) within an administrative unit, (3) within a program area, and (4) within an academic department or school. The interviews addressed the philosophy and approach to program evaluation, what evaluators do, the perceived effects of organizational structure on evaluation, and reflections on the optimal structure for program evaluation in Extension. Several conclusions are presented: the evaluation function should be associated with a high administrative level in the organization, locating the evaluation function in program units appears to be preferred, roles and responsibilities of internal evaluators need to be clearly specified, internal evaluators need to work closely with administration and management to carry out their roles effectively and to incorporate evaluation into organizational decision making, and internal evaluators often assume other roles beyond their primary role as evaluator. © Wiley Periodicals, Inc.
EBV‐encoded LMP1 regulates Op18/stathmin signaling pathway by cdc2 mediation in nasopharyngeal carcinoma cells
Authors: Lin Xuechi , Liu Sufang , Luo Xiangjian , Ma Xiaoqian , Guo Lili , Li Lili , Li Zijian , Tao Yongguang , Cao Ya
Published: December 2008

Oncoprotein 18/stathmin (Op18/stathmin) plays a crucial role in maintaining cell biological characteristics by regulating microtubule dynamics, especially entry into mitosis; phosphorylated Op18/stathmin promotes microtubule polymerization to form the mitotic spindle, which is essential for chromosome segregation and cell division. Cdc2 is a critical kinase in starting M phase events in cell‐cycle progression and is a positive regulator of the cell cycle. Latent membrane protein 1 (LMP1) is an Epstein‐Barr virus (EBV)‐encoded oncogenic protein that is able to induce carcinogenesis via various signaling pathways. This study focused on regulation by LMP1 of Op18/stathmin signaling in nasopharyngeal carcinoma (NPC) cells and showed that LMP1 regulates Op18/stathmin signaling through cdc2 mediation, LMP1 upregulates cdc2 kinase activity, and Op18/stathmin phosphorylation promotes the interaction of cdc2 with Op18/stathmin and microtubule polymerization during mitosis, and inhibition of LMP1 expression attenuates the interaction of cdc2 and Op18/stathmin and promotes microtubule depolymerization. These results reveal a new pathway via which LMP1 regulates Op18/stathmin signaling by cdc2 mediation; this new signaling pathway not only perfects the LMP1 regulation network but also elucidates the molecular mechanism of LMP1 that leads to carcinogenesis. © 2008 Wiley‐Liss, Inc.
Selective targeting by preS1 domain of hepatitis B surface antigen conjugated with phosphorylcholine‐based amphiphilic block copolymer micelles as a biocompatible, drug delivery carrier for treatment of human hepatocellular carcinoma with paclitaxel
Authors: Miyata Ryohei , Ueda Masakazu , Jinno Hiromitsu , Konno Tomohiro , Ishihara Kazuhiko , Ando Nobutoshi , Kitagawa Yuko
Published: December 2008

Using dithioester‐capped 2‐methacryloyloxyethyl phosphorylcholine (MPC) as a macro chain transfer agent, a diblock copolymer was synthesized with n‐butyl methacrylate (BMA) as hydrophobic core‐forming blocks. The MPC–BMA unit was copolymerized with an immobilizable unit, p‐nitrophenylcarbonyloxyethyl methacrylate (NPMA). The NPMA moiety then was modified by the addition of preS1 domain of hepatitis B surface antigen (HBsAg). This micelle‐forming nanoparticle, the poly (MPC‐co‐BMA‐co‐NPMA) (PMBN) conjugated with preS1 enables solubilization of paclitaxel (PTX) with increased hepatotropism. The 50% inhibitory concentration (IC50) values of PTX and PTX/PMBN‐preS1 against the human hepatocellular carcinoma cell line, HepG2, were 1,008 and 131 nM, respectively (p < 0.05). Conjugation of preS1 to PMBN enhanced strongly the synergistic inhibitory effect of paclitaxel on HepG2 cells in vitro, whereas such a change in IC50 was not detected against the human squamous cell carcinoma cell line, A431. Tumor growth rates of a HepG2 xenograft in Balb/c nude mice after intraperitoneal injection of PTX, PTX/PMBN and PTX/PMBN‐preS1 were +97.9%, −74.3% and −96.2%*, respectively (*p < 0.05 versus PTX). The local paclitaxel levels after administration of the PMBN‐preS1 conjugate were determined in the xenografts by high‐performance liquid chromatography and were 8 times higher than that after administration of paclitaxel alone. No side effects attributable to PMBN‐preS1 were observed histologically in vital organs, and body weight loss was significantly less in the PTX/PMBN‐preS1 group. These studies demonstrate that PMBN‐preS1 may be used as a human hepatocyte‐specific drug delivery carrier without serious adverse effects. © 2008 Wiley‐Liss, Inc.
Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a large prospective study, from 1996 to 2006
Authors: Dorjgochoo Tsogzolmaa , Shu Xiao‐Ou , Li Hong‐Lan , Qian Han‐Zhu , Yang Gong , Cai Hui , Gao Yu‐Tang , Zheng Wei
Published: December 2008

The association of contraceptive methods, including oral contraceptives (OC), intrauterine devices (IUD) and tubal sterilization (TS), with overall and site‐specific cancer were prospectively investigated in a cohort of 66,661 Chinese women in Shanghai, 76.7% of whom used contraception. During a median follow‐up time of 7.5 years, 2,250 women were diagnosed with cancer. Ever‐use of any contraceptive method was not associated with overall cancer risk [adjusted hazard ratio (HRadj) = 1.02, 95% CI, 0.92–1.12]. Use of any contraceptive method was associated with increased risk of rectal cancer (HRadj = 1.68, 95% CI, 1.08–2.62) and reduced risk of thyroid cancer (HRadj = 0.63, 95% CI, 0.38–1.04). Risk of gallbladder cancer increased with ever use of OC (HRadj = 2.38, 95% CI, 1.26–4.49). IUD use was associated with a possible reduced risk of thyroid cancer (HRadj = 0.64, 95% CI, 0.38–1.07). Longer duration of IUD use decreased risk for breast, thyroid and lung cancers. Ever having a TS was associated with increased uterine body cancer (HRadj = 2.50, 95% CI, 1.47–4.25) and decreased risk of stomach cancer (HRadj = 0.59, 95% CI, 0.39–0.91). We did not find any contraceptive method to be related to the risk of ovarian cancer but the analyses were based on few events. Although chance findings are a likely explanation for some of the associations found in our study, these findings suggest that various contraceptive methods or reproductive patterns may play a role in the etiology of cancer. © 2008 Wiley‐Liss, Inc.
Large differences in patterns of breast cancer survival between Australia and England: A comparative study using cancer registry data
Authors: Woods Laura M. , Rachet Bernard , O'Connell Dianne , Lawrence Gill , Tracey Elizabeth , Willmore Alan , Coleman Michel P.
Published: December 2008

Survival from breast cancer in the UK is lower than in other countries in Western Europe, the USA and Australia. However, these international differences have not yet been examined in relation to tumor characteristics, treatment, screening history or other prognostic factors. We calculated relative survival by age, period of diagnosis, category of unemployment and extent of disease for women diagnosed with breast cancer during the period 1980–2002 in New South Wales (Australia) and West Midlands (England). National cancer registry data for each country for the period 1990–1994 were also examined. The excess hazard ratio was modeled as a function of prognostic covariables. Survival in Australia and New South Wales was higher than in England and West Midlands, respectively. In both regions, survival was lower for more deprived women and for the elderly. These differences were greater in West Midlands. Survival from localized and regional disease in New South Wales was higher than in West Midlands, but survival from metastatic disease was similar. Differences in breast cancer survival are unlikely to be entirely due to differences in data quality or to limitations of the analyses, although the measure of extent of disease used may not have been adequate to elucidate the effect of stage fully. One possible causal explanation is that the management of breast cancer differs between these regions. Further research should acquire better data on stage and investigate the effect of comorbidity and of patterns of care upon the difference in breast cancer survival between England and Australia. © 2008 Wiley‐Liss, Inc.
Efficient eradication of hormone‐resistant human prostate cancers by inactivated Sendai virus particle
Authors: Kawaguchi Yoshifumi , Miyamoto Yasuhide , Inoue Takehiro , Kaneda Yasufumi
Published: December 2008

Hormone‐refractory prostate cancer is one of the intractable human cancers in the world. Here, we examined the direct tumor‐killing activity of inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ‐E)] through induction of Type I interferon (IFN) in the hormone‐resistant human prostate cancer cell lines PC3 and DU145. Preferential binding of HVJ‐E to PC3 and DU145 over hormone‐sensitive prostate cancer cell and normal prostate epithelium was observed, resulting in a number of fused cells. After HVJ‐E treatment, a number of IFN‐related genes were up‐regulated, resulting in Type I IFN production in PC3 cells. Then, retinoic acid‐inducible gene‐I (RIG‐I) helicase which activates Type I IFN expression after Sendai virus infection was up‐regulated in cancer cells after HVJ‐E treatment. Produced IFN‐α and ‐β enhanced caspase 8 expression via Janus kinases/Signal Transducers and Activators of Transcription pathway, activated caspase 3 and induced apoptosis in cancer cells. When HVJ‐E was directly injected into a mass of PC3 tumor cells in SCID (severe combined immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was observed and 85% of the mice became tumor‐free. Although co‐injection of an anti‐asialo GM1 antibody with HVJ‐E into each tumor mass slightly attenuated the tumor suppressive activity of HVJ‐E, significant suppression of tumor growth was observed even in the presence of anti‐asialo GM1 antibody. This suggests that natural killer cell activation made small contribution to tumor regression following HVJ‐E treatment in hormone‐resistant prostate cancer model in vivo. Thus, HVJ‐E effectively targets hormone‐resistant prostate cancer by inducing apoptosis in tumor cells, as well as activating anti‐tumor immunity. © 2009 Wiley‐Liss, Inc.
Melanoma‐associated chondroitin sulphate proteoglycan as a new target antigen for CD4+ T cells in melanoma patients
Authors: Erfurt Cornelia , Müller Esther , Emmerling Sonja , Klotz Claudia , Hertl Michael , Schuler Gerold , Schultz Erwin S.
Published: December 2008

Melanoma‐associated chondroitin sulfate proteoglycan (MCSP) (also known as high molecular weight‐melanoma‐associated antigen) represents an interesting target antigen for cancer immunotherapy which is expressed on human melanomas and other tumors such as breast carcinomas, gliomas, neuroblastomas and acute leukemias. MCSP seems to play an important functional role in melanoma as it is involved in tumor cell migration, invasion and angiogenesis. In this study, we isolated CD4+ T helper cells from the blood of a healthy donor, recognizing a peptide from the MCSP core protein presented by HLA‐DBR1*1101 molecules. T cell reactivity against the identified peptide could be detected in the blood of healthy donors and melanoma patients. MCSP specific T cells from the blood of a patient could be readily expanded by repeated peptide stimulation and recognized MCSP and HLA‐DR expressing tumor cells. Our findings suggest that vaccination against MCSP helper T cell epitopes might be a promising approach to fight melanoma. © 2009 Wiley‐Liss, Inc.
A thermosensitive chitosan/poly(vinyl alcohol) hydrogel containing hydroxyapatite for protein delivery
Authors: Tang Yufeng , Du Yumin , Li Yan , Wang Xiaoying , Hu Xianwen
Published: December 2008

The synthesis and characterization of a thermosensitive chitosan/poly(vinyl alcohol) (PVA) hydrogel containing hydroxyapatite for protein delivery were first reported. Two synthetic processes were introduced, that is, in situ and ex situ routes. Fourier‐transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and rheological analysis were employed to characterize the hydrogel. The gel formation decreased the crystallinity of the hydroxyapatite crystal. FTIR results showed that the hydroxyapatite crystals were partially substituted by carbonate. It was supposed that the structural features of hydroxyapatite were close to those of biological apatites. The thermosensitive property of the gels was evaluated by rheological analysis, which indicated that the strength of hydroxyapatite–chitosan/PVA composite gels was notably enhanced in comparison with that of pure chitosan/PVA gel, especially for hydroxyapatite–chitosan/PVA composite gels synthesized through the in situ process. The performances of composite gels containing different amounts of hydroxyapatite were further studied. For the hydroxyapatite–chitosan/PVA composite gels containing 0.1 mM hydroxyapatite synthesized through in situ process, the swelling degree was the lowest, and the speed of protein release was the slowest. Therefore, the composite gels are attractive for applications as protein delivery, artificial bones, and scaffolds for tissue engineering. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Minor pathological changes are induced by naltrexone‐poly(DL‐lactide) implants in pregnant rats
Authors: Farid W. O. , McCallum D. , Tait R. J. , Dunlop S. A. , Hulse G. K.
Published: December 2008

Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained‐release preparations have been developed to overcome noncompliance. Many sustained‐release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow‐release subcutaneous naltrexone‐poly (DL‐lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans‐3,6‐dimethyl‐1,4‐dioxyane‐2,5‐dione] (DL‐lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13–26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose‐dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low‐level inflammation, suggested good long‐term biocompatibility. We conclude that the Australian naltrexone‐poly(DL‐lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Sox9 expression of alginate‐encapsulated chondrocytes is stimulated by low cell density
Authors: Bernstein Peter , Dong Meng , Graupher Sylvi , Corbeil Denis , Gelinsky Michael , Günther Klaus‐Peter , Fickert Stefan
Published: December 2008

Recent research in tissue engineering for the treatment of cartilage defects have demonstrated that matrix‐biomaterial, cell culture conditions, and cytokine‐related factors influence the chondrogenic differentiation pattern, especially for the expression of matrix genes. However, little is known about the impact of cell seeding density in a three‐dimensional environment on the key chondrogenic transcription factor Sox9. Here we investigated, whether the cell concentration of alginate encapsulated chondrocytes influences the Sox9 expression. Dedifferentiated passage‐4 porcine chondrocytes were encapsulated in alginate beads at two different concentrations (4 × 106versus 7 × 107cells/mL) and cultivated for up to 4 weeks under TGF‐ß stimulation. The expression of Sox9, Collagen I, II, and X was assessed via quantitative RT‐PCR and compared to those observed in the initial monolayer culture. Cellular viability, cell morphology, and the sulphated glycosaminoglycan‐production were monitored. Interestingly Sox9 expression was significantly upregulated in the low‐cell‐density group, whereas no difference between high‐cell‐density and monolayer culture group could be observed. Furthermore, the cellular survival and the sulphated glycosaminoglycan production were higher in the low‐cell‐density group. Collagen I expression was downregulated in the low‐cell‐density group whereas it was upregulated in the high‐cell‐density one. Surprisingly, only the high‐cell‐density group showed the expression of Collagen II, although it appeared not significant. Collagen X expression was upregulated in the low‐cell‐density group. Taken together our data indicate that a low concentration of cell seeding in a three‐dimensional environment is beneficial for the overall chondrogenic development. However, this article reveals discrepancies between Sox9 and the chondrogenic pathway in redifferentiating chondrocytes that should be addressed in further work. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Oxygen diffusivity of biologic and synthetic scaffold materials for tissue engineering
Authors: Valentin Jolene E. , Freytes Donald O. , Grasman Jonathan M. , Pesyna Colin , Freund John , Gilbert Thomas W. , Badylak Stephen F.
Published: December 2008

Scaffolds for tissue engineering and regenerative medicine applications are commonly manufactured from synthetic materials, intact or isolated components of extracellular matrix (ECM), or a combination of such materials. After surgical implantation, the metabolic requirements of cells that populate the scaffold depend upon adequate gas and nutrient exchange with the surrounding microenvironment. The present study measured the oxygen transfer through three biologic scaffold materials composed of ECM including small intestinal submucosa (SIS), urinary bladder submucosa (UBS), and urinary bladder matrix (UBM), and one synthetic biomaterial, Dacron™. The oxygen diffusivity was calculated from Fick's first law of diffusion. Each material permitted measurable oxygen diffusion. The diffusivity of SIS was found to be dependent on the direction of oxygen transfer; the oxygen transfer in the abluminal‐to‐luminal direction was significantly greater than the luminal‐to‐abluminal direction. The oxygen diffusivity of UBM and UBS were similar despite the presence of an intact basement membrane on the luminal surface of UBM. Dacron showed oxygen diffusivity values seven times greater than the ECM biomaterials. The current study showed that each material has unique oxygen diffusivity values, and these values may be dependent on the scaffold's ultrastructure. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Proteomic analysis of mitochondrial proteins of basal and lipolytically (isoproterenol and TNF‐α)‐stimulated adipocytes
Authors: Cho Si Young , Park Pil Joon , Shin Eui Seok , Lee Jung Ho , Chang Hui Kyoung , Lee Tae Ryong
Published: December 2008

The regulation of adipocyte lipolysis is increasingly believed to influence insulin resistance, in a process that may be associated with mitochondrial dysfunction. However, the molecular basis of the relationship between mitochondrial protein expression, lipolytic responsiveness, and insulin resistance remains unknown. A set of proteins that shows altered abundances in the mitochondria of untreated and treated 3T3‐L1 adipocytes with TNF‐α or isoproterenol was identified. These include the proteins associated with energy production, including fatty acid oxidation, TCA cycle, and oxidative phosphorylation. Proteins associated with oxidative stress dissipation were down‐regulated in lipolytically stimulated adipocytes. Lipolytic stimulation with isoproterenol and TNF‐α, which is also a potent proinflammatory cytokine, showed some noticeable differences in mitochondrial protein expression. For example, isoproterenol markedly enhanced the expression of prohibitin which is involved in the integrity of mitochondria but TNF‐α did not. These results provide valuable information on mitochondrial dysfunction associated with oxidative stress induced by lipolytic stimulation. J. Cell. Biochem. 106: 257–266, 2009. © 2008 Wiley‐Liss, Inc.
Microfilament and microtubule assembly is required for the propagation of inositol trisphosphate receptor‐induced Ca2+ waves in bovine aortic endothelial cells
Authors: Béliveau Éric , Guillemette Gaétan
Published: December 2008

Ca2+ is a highly versatile second messenger that plays a key role in the regulation of numerous cell processes. One‐way cells ensure the specificity and reliability of Ca2+ signals is by organizing them spatially in the form of waves that propagate throughout the cell or within a specific subcellular region. In non‐excitable cells, the inositol 1,4,5‐trisphosphate receptor (IP3R) is responsible for the release of Ca2+ from the endoplasmic reticulum. The spatial aspect of the Ca2+ signal depends on the organization of various elements of the Ca2+ signaling toolkit and varies from tissue to tissue. Ca2+ is implicated in many of endothelium functions that thus depend on the versatility of Ca2+ signaling. In the present study, we showed that the disruption of caveolae microdomains in bovine aortic endothelial cells (BAEC) with methyl‐ß‐cyclodextrin was not sufficient to disorganize the propagation of Ca2+ waves when the cells were stimulated with ATP or bradykinin. However, disorganizing microfilaments with latrunculin B and microtubules with colchicine both prevented the formation of Ca2+ waves. These results suggest that the organization of the Ca2+ waves mediated by IP3R channels does not depend on the integrity of caveolae in BAEC, but that microtubule and microfilament cytoskeleton assembly is crucial. J. Cell. Biochem. 106: 344–352, 2009. © 2008 Wiley‐Liss, Inc.
The polyamine analogue N1,N11‐diethylnorspermine can induce chondrocyte apoptosis independently of its ability to alter metabolism and levels of natural polyamines
Authors: Stanic' Ivana , Facchini Annalisa , Borzì Rosa Maria , Stefanelli Claudio , Flamigni Flavio
Published: December 2008

We have been investigating the effects of natural polyamines and polyamine analogues on the survival and apoptosis of chondrocytes, which are cells critical for cartilage integrity. Treatment of human C‐28/I2 chondrocytes with N1,N11‐diethylnorspermine (DENSPM), a polyamine analogue with clinical relevance as an experimental anticancer agent, rapidly induced spermidine/spermine N1‐acetyltransferase (SSAT) and spermine oxidase (SMO), key enzymes of polyamine catabolism and down‐regulated ornithine decarboxylase, the first enzyme of polyamine biosynthesis, thus depleting all main polyamines within 24 h. The treatment with DENSPM did not provoke cell death and caspase activation when given alone for 24 h, but caused a caspase‐3 and ‐9 dependent apoptosis in chondrocytes further exposed to cycloheximide (CHX). In other cellular models, enhanced polyamine catabolism or polyamine depletion has been implicated as mechanisms involved in DENSPM‐related apoptosis. However, the simultaneous addition of DENSPM and CHX rapidly increased caspase activity in C‐28/I2 cells in the absence of SSAT and SMO induction or significant reduction of polyamine levels. Moreover, caspase activation induced by DENSPM plus CHX was not prevented by a N1‐acetylpolyamine oxidase (PAO)/SMO inhibitor, and depletion of all polyamines obtained by specific inhibitors of polyamine biosynthesis did not reproduce DENSPM effects in the presence of CHX. DENSPM/CHX‐induced apoptosis was associated with changes in the amount or activation of signalling kinases, Akt and MAPKs, and increased uptake of DENSPM. In conclusion, the results suggest that DENSPM can favour apoptosis in chondrocytes independently of its effects on polyamine metabolism and levels. J. Cell. Physiol. 219: 109–116, 2009. © 2008 Wiley‐Liss, Inc.
Computational and experimental optimization of a double‐tuned 1H/31P four‐ring birdcage head coil for MRS at 3T
Authors: Duan Yunsuo , Peterson Bradley S. , Liu Feng , Brown Truman R. , Ibrahim Tamer S. , Kangarlu Alayar
Published: December 2008

Purpose

To optimize the homogeneity and efficiency of the B1 magnetic field of a four‐ring birdcage head coil that is double‐tuned at the Larmor frequencies of both 31P and 1H and optimized to acquire magnetic resonance spectroscopy (MRS) data at 3T for the study of infants.

Materials and Methods

We developed a finite difference time domain (FDTD) tool in‐house to iteratively compute and seek the range of geometric and electromagnetic parameters of a dual‐tuned, four‐ring birdcage coil that would produce the desired resonance patterns, optimize homogeneity of the B1‐field, and maximize efficiency of the coil. To demonstrate the validity of our computational results, we constructed three RF coils: one dual‐tuned coil that was based on the calculated optimized parameters and two single‐tuned coils that had dimensions similar to those of the dual‐tuned coil, but tuned at the Larmor frequencies of both 31P and 1H, respectively. We then tested and compared the performances of the dual‐tuned coil and single‐tuned coils at both of these frequencies.

Results

We found that a dual‐tuned, four‐ring birdcage coil with a diameter of 180 mm, an inner birdcage length of 100–300 mm, and an outer birdcage length of 25–100 mm produces the desired resonance patterns. For the use of this coil with human infants, optimization of the homogeneity of the B1 field, combined with improved coil efficiency, yielded a dual‐tuned birdcage coil with diameter of 180mm, an inner birdcage length of 150 mm, an outer birdcage length of 25 mm, and corresponding inner and outer capacitances of 17.2 pF and 7.6 pF, respectively. The experimental results from a constructed coil having the sameparameters with the modeled coil agreed well with the computational results from the modeled coil. This optimized design overcame the deficiencies of existing dual‐tuned, four‐ring birdcage coils.

Conclusion

The homogeneity and efficiency of the B1 field for 31P/1H dual‐tuned, four‐ring birdcage coils can be optimized well using our FDTD tool, especially at high static magnetic fields (B0). J. Magn. Reson. Imaging 2009;29:13–22. © 2008 Wiley‐Liss, Inc.
Diffusion measurements and diffusion tensor imaging with noisy magnitude data
Authors: Kristoffersen Anders
Published: December 2008

Purpose

To compare an unbiased method for estimation of the diffusion coefficient to the quick, but biased, log‐linear (LL) method in the presence of noisy magnitude data.

Materials and Methods

The magnitude operation changes the signal distribution in magnetic resonance (MR) images from Gaussian to Rician. If not properly taken into account, this will introduce a bias in the estimated diffusion coefficient. We compare two methods by means of Monte Carlo simulations. The first one applies least‐squares fitting of the measured signal to the median (MD) value of the probability density function. The second method is uncorrected LL estimation. We also perform a high‐resolution diffusion tensor experiment.

Results

The uncorrected LL estimator is heavily biased at low signal‐to‐noise ratios. The bias has a significant effect on image quality. The MD estimator is accurate and produces images with excellent contrast.

Conclusion

In the presence of noisy magnitude data, unbiased estimation is essential in diffusion measurements and diffusion tensor imaging. J. Magn. Reson. Imaging 2009;29:237–241. © 2008 Wiley‐Liss, Inc.
New coil positioning method for interleaved transcranial magnetic stimulation (TMS)/functional MRI (fMRI) and its validation in a motor cortex study
Authors: Moisa Marius , Pohmann Rolf , Ewald Lars , Thielscher Axel
Published: December 2008

Purpose

To develop and test a novel method for coil placement in interleaved transcranial magnetic stimulation (TMS)/functional MRI (fMRI) studies.

Materials and Methods

Initially, a desired TMS coil position at the subject's head is recorded using a neuronavigation system. Subsequently, a custom‐made holding device is used for coil placement inside the MR scanner. The parameters of the device corresponding to the prerecorded position are automatically determined from a fast structural image acquired directly before the experiment. The spatial accuracy of our method was verified on a phantom. Finally, in a study on five subjects, the coil was placed above the cortical representation of a hand muscle in M1 and the blood oxygenation level‐dependent (BOLD) responses to short repetitive TMS (rTMS) trains were assessed using echo‐planar imaging (EPI) recordings.

Results

The spatial accuracy of our method is in the range of 2.9 ± 1.3 (SD) mm. Motor cortex stimulation resulted in robust BOLD activations in motor‐ and auditoryrelated brain areas, with the activation in M1 being localized in the hand knob.

Conclusion

We present a user‐friendly method for TMS coil positioning in the MR scanner that exhibits good spatial accuracy and speeds up the setup of the experiment. The motor‐cortex study proves the viability of the approach and validates our interleaved TMS/fMRI setup. J. Magn. Reson. Imaging 2009;29:189–197. © 2008 Wiley‐Liss, Inc.
Diagnostic utility of diffusion‐weighted MR imaging and apparent diffusion coefficient value for the diagnosis of adrenal tumors
Authors: Tsushima Yoshito , Takahashi‐Taketomi Ayako , Endo Keigo
Published: December 2008

Purpose

To determine the utility of diffusion‐weighted MR imaging (DWI) for the diagnosis of adrenal tumors.

Materials and Methods

Forty‐two patients (24 men and 18 women; age, 61.5 ± 12.7 years old; range, 34–86 years) with 43 adrenal tumors (11 functioning cortical adenomas, 20 nonfunctioning cortical adenomas, 7 metastatic tumors, and 5 pheochromocytomas) were retrospectively investigated. DWIs were obtained by single‐shot spin‐echo type echo‐planar imaging sequence (1.5 Tesla [T]; TR = 8000 ms, TE = 72, b‐factor = 0 and 1000 s/mm2), and apparent diffusion coefficient (ADC) value was calculated. Chemical shift images were obtained by gradient echo sequence (TR = 161, TE = 2.38 [out‐of‐phase, OP] and 4.76 [in‐phase, IP], FA = 60), and the signal intensity index (SII; [IP‐OP]/IP *100%) was calculated.

Results

There was no difference in ADC values between adenomas (1.09 ± 0.29*10−3 mm2/s; range, 0.52–1.64) and metastatic tumors (0.85 ± 0.26*10−3; 0.51–1.23; p = 0.14). Pheochromocytomas showed the higher mean ADC value (1.59 ± 0.34*10−3; 1.04–1.96) compared with those of adenomas or metastatic tumors (P < 0.05 and P < 0.005, respectively). The mean SII of adenomas (62.1 ± 17.9%; 14.5–88.4) was significantly higher than those of pheochromocytomas (4.0 ± 10.0%; −19.6–3.3; P < 0.005) or metastatic tumors (−1.5 ± 11.7%; −18.3–8.2; P < 0.01). There was no correlation between ADC values and SII.

Conclusion

Although pheochromocytomas showed higher ADC values, we did not find that ADC value had diagnostic utility for differentiating adenomas and metastatic tumors. J. Magn. Reson. Imaging 2009;29:112–117. © 2008 Wiley‐Liss, Inc.