bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrete equivalent time integration methods for transient analysis
Authors: Muǧan Ata
Published: July 2003

It was recently shown in a series of papers that the frequency response of temporally discretized finite element equations and, consequently, the achievable accuracy cannot be manipulated independently in different frequency ranges. In addition, there exist limitations on the achievable accuracy of a time integration method no matter what the order of accuracy of the method is. Motivated by this fact, a family of time integration methods is derived in the time domain based on the principle that the exact solution of the semidiscrete equation of a system and the solution of the time integration method match at discrete time steps. It is necessary to pursue an exact match at discrete time steps, i.e. discrete equivalence, since the solutions of semidiscrete equations are obtained only at the time steps. Two time integration methods, that are exact at the time steps, are obtained based on the impulse and ramp response invariance principles. Numerical examples are presented to show the advantage of the proposed methods and to compare the performance of them with the performance of some popular methods. Copyright © 2003 John Wiley & Sons, Ltd.
Curved quadratic triangular degenerated‐ and solid‐shell elements for geometric non‐linear analysis
Authors: Kim C. H. , Sze K. Y. , Kim Y. H.
Published: July 2003

Compared to the large number of curved quadrilateral degenerated‐ and solid‐shell elements, there are only a very few curved triangular degenerated‐ and solid‐shell elements. Based on the assumed natural strain sampling scheme previously developed for a quadratic degenerated‐shell element for linear analysis, this paper devises geometric non‐linear six‐node degenerated‐shell and twelve‐node solid‐shell elements. Both elements can be curved and are only equipped with the standard nodal d.o.f.s. Careful consideration has been exercised to circumvent various locking phenomena that plague degenerated‐ and solid‐shell elements. Numerical examples are presented to illustrate their efficacy. Copyright © 2003 John Wiley & Sons, Ltd.
Extension of a paediatric diabetes home care service
Authors: Kirk J , Thomas E , McEvilly A , Shaw N
Published: July 2003

At the end of 1994 a paediatric diabetes specialist nurse (PDSN) was appointed to extend the paediatric diabetes home care service between the Birmingham Children's Hospital and a district general hospital (City Hospital) in Birmingham. As a result 24‐hour home care can now be offered to newly diagnosed and existing paediatric patients with diabetes at City Hospital. The initial mean HbA1c for the clinic was 9.8%, which since then has fallen to a mean of 8.95% (range 7.9–9.4%); a mean reduction of 0.85%. As a result of home care there has been a sustained reduction in bed‐days for newly diagnosed patients (median five patients per year) and for re‐admissions of existing patients. In addition to any long‐term benefits arising from improvement in diabetic control, the cost savings of reduction in bed‐days alone at £235 per day (Total £15110 per year) outweigh the cost of the PDSN post (£14800 per year). Copyright © 2003 John Wiley & Sons, Ltd.
A countywide primary care annual audit fails to demonstrate an improvement in diabetes care between 1996 and 2001
Authors: Masding MG , Adams A , Dawson A , Gatling W
Published: July 2003

Multipractice audit is widely used and can affect diabetes care. We reviewed the Dorset diabetes audit between 1996 and 2001 to investigate the prevalence of diabetes and to examine if the processes of diabetes care change over time.

Data on prevalence of diabetes and the numbers of patients who underwent annual diabetes review, foot and eye screening, and measurement of blood pressure (BP), creatinine and HbA1c was obtained from 102 out of 109 Dorset general practices (involving a total population of 663466 people) on an annual basis between 1996 and 2001.

The prevalence of diabetes rose from 2.34% (95% CI 2.30, 2.37) in 1996/97 to 2.59% (2.55, 2.63) in 2000/01. The proportion of patients undergoing the process of diabetes care fell slightly over the five years: annual review 92.7% (92.1, 93.3) to 85.0% (84.4, 85.6), p<0.001; foot review 80.5% (79.9, 81.1) to 71.7% (71.0, 72.4), p<0.001; eye review 76.7% (75.9, 77.5) to 65.5% (64.8, 66.2), p<0.001; BP measurement 89.8% (89.2, 90.5) to 86.7% (86.1, 87.2), p<0.001; creatinine measurement 84.0% (83.3, 84.7) to 80.1% (79.5, 80.7), p<0.001; HbA1c measurement 88.4% (87.8, 88.0) to 86.3% (85.8, 86.8), p<0.001.

The prevalence of diabetes in Dorset rose significantly between 1996 and 2001, adversely affecting diabetes complication screening rates. Screening rates for diabetes complications deteriorated over the five years of our study, after an initial rise when the audit was newly established. Alternative strategies to improve diabetes care may be necessary to change clinical practice. Copyright © 2003 John Wiley & Sons, Ltd.
Islet transplant – a secure future for cellular replacement therapy in diabetes
Authors: Shapiro AMJ , Lakey JRT
Published: July 2003

Outcomes in clinical islet transplantation have recently been transformed, following the introduction of steroid‐free, sirolimus based immunosuppression and the development of more refined methods for islet isolation from the donor pancreas. With the ‘Edmonton Protocol’, currently 85% of patients (28 completed transplants) remain free of insulin at the one year time‐point, and three in four patients remain free beyond three years. Variants of this protocol have now been successfully replicated in over 150 patients worldwide. Complete normalisation of glycated haemoglobin suggests that this therapy is likely to prevent, stabilise and possibly reverse early complications of diabetes. Progress with single donor islet transplant will allow many more patients with type 1 diabetes to be treated, but will fail to meet the enormous demand for this type of therapy.

Development of safer, low‐dose anti‐rejection therapies with very low risk of cancer or infectious complications is likely to further broaden the indications for islet transplant therapy in diabetes. If tolerance (or near‐tolerance) could be safely induced, protecting against both autoimmune and alloimmune rejection, then islet transplantation could possibly be applied in children, possibly allowing the use of laparoscopic live donor distal pancreatectomy to expand the available donor source. Recent progress both in stem cell biology and in xenotransplantation suggests that ultimately a limitless source of insulin secreting tissues will be found. The light at the end of the tunnel for patients with type 1 diabetes just got brighter. Copyright © 2003 John Wiley & Sons, Ltd.
Advances in islet transplantation and the UK islet transplant consortium
Authors: Paget MB , Downing R
Published: July 2003

Islet transplantation has surpassed whole pancreas transplantation as a cure for diabetes mellitus since the success of the Edmonton group. It is a safer procedure and requires minimal surgical intervention, yet offers excellent results in terms of achieving insulin independence. It also offers a more physiological insulin profile than current insulin replacement therapy. The UK Islet Transplant Consortium, founded by Diabetes UK, is in the process of establishing a programme of clinical islet transplantation in the UK.

The immunosuppression required to protect islet grafts remains a threat to the long‐term health of transplant recipients and research into the possibility of circumventing the need for immunosuppression continues. The main areas under investigation include immunoisolation of islet grafts, HLA class II mismatching between donor and recipient, destruction of immune‐reactive dendritic cells in culture, in vitro pre‐treatment of islets to reduce their immunogenicity and genetic modification of islets to produce localised immunosuppression and prevent the release of MHC molecules.

Because of the shortage of donors, researchers are looking toward alternative sources of glucose‐responsive insulin‐secreting tissue. Xenotransplantation would offer an attractive solution if the risk of transferring animal endogenous retroviruses can be eliminated. The expansion of mature beta‐cells, beta‐cell progenitors in pancreatic ducts or embryonic stem cells into viable tissue for transplant is also being researched in the hope of finding a solution for the tissue shortage issue. Encouraging advances have been made in many of these areas, creating a sense of anticipation and excitement for the future. Copyright © 2003 John Wiley & Sons, Ltd.
The low carbohydrate diet—personal experience in type 2 diabetes
Authors: Arnold Michael
Published: July 2003

Following the low‐carbohydrate diet, defined by Drs Berstein, Eades and Atkins, I have lost 23% of my body weight and my blood sugar, total cholesterol and HbA1chave all fallen. I have also been able to taper off my diabetes medication. This article summarises my experience with this dietary approach. Copyright © 2003 John Wiley & Sons, Ltd.
The low carbohydrate/low insulin regimen – personal experience in type 1 diabetes
Authors: Raab Ron
Published: July 2003

In this article, I describe my before and after experience in adopting a low carbohydrate/low insulin/moderate protein/appropriate fat approach to the management of my type 1 diabetes. The Diabetes Centre in New York specialises in this approach and this article is based on what I learnt there and have applied since June 1998. I outline the rationale for and advantages of this approach and the contradictions inherent in the high carbohydrate/high insulin approach. These are my personal views and do not represent the position of organisations with which I work. Copyright © 2003 Ron Raab.
Carbohydrate intake in diabetes: how much is optimal?
Authors: Troughton Jacqui
Published: July 2003

Nutritional advice that has little or no supporting evidence is still being given to people with diabetes. Advice pertaining to carbohydrate can be misleading. People with diabetes need evidence‐based information about carbohydrates and to be given the knowledge and skills necessary to adjust their lifestyle, medication and/or insulin around the choices they wish to make. Copyright © 2003 John Wiley & Sons, Ltd.
Parallel clinical course of diabetes in a husband and wife with type 2 diabetes
Authors: Chowdhury TA , Lasker SS
Published: July 2003

A 50‐year‐old South Asian man was diagnosed with type 2 diabetes on a routine test. He found his wife to have diabetes shortly afterwards. Baseline clinical findings at diagnosis were similar in the husband and wife. Over the course of the next seven years, there was a remarkable similarity in the clinical course of the spouses' glycaemic control, blood pressure control, weight and, most recently, the onset of microvascular complications. This is the first report of such marked similarity in the clinical course of diabetes in spouses, and suggests that environmental factors may be important in the progression of type 2 diabetes. Copyright © 2003 John Wiley & Sons, Ltd.
Thermal and electrical effects caused by outdoor hot‐spot testing in associations of photovoltaic cells
Authors: García M. C. Alonso , Herrmann W. , Böhmer W. , Proisy B.
Published: July 2003

An outdoor test facility has been prepared for the evaluation of the thermal and electrical effects caused by outdoor hot‐spot testing in crystalline silicon modules. Five module types have been subjected to an outdoor test programme with the purpose of analysing their hot‐spot endurance. The worst‐case cell in each module type has been detected by laboratory characterisation under reverse‐bias operation of all the individual cells included in the module. These cells, encapsulated within the module, have been operated at different shading fractions with bypass diodes around 18 or 24 cells. A data acquisition system has monitored temperatures and current flows during the day, completing the tests via infrared characterisation during the hours of maximum irradiance. The influence of the type of module, the number of cells per bypass diode, the position and amount of shading and the leakage current of the cell is presented. This information is useful for cell and module manufacturers and system installers who must select the necessary protection criteria to guarantee long lifetimes for PV systems; it also helps to clarify hot‐spot testing procedures in international standards. Copyright © 2003 John Wiley & Sons, Ltd.
Local series resistance mapping of silicon solar cells by microwave photoconductivity decay measurements
Authors: Ballif C. , Peters S. , Borchert D.
Published: July 2003

We present a new non‐destructive mapping technique which yields information on the local series resistance in Si solar cells. The technique is based on microwave photoconductivity decay measurements performed on reverse‐biased Si solar cells. For reverse‐biased devices, the initial decay time measured after a high‐intensity laser pulse is shown to be directly proportional to the local series resistances between the excited area and the cell metallisation. We illustrate how high contact resistance between the fingers and the emitter, resistive back‐surface contacts or finger interruptions lead to an increase of the microwave detected decay time. Copyright © 2003 John Wiley & Sons, Ltd.
Cu(In,Ga)Se2thin films grown with a Cu‐poor/rich/poor sequence: growth model and structural considerations
Authors: Kessler J. , Chityuttakan C. , Lu J. , Schöldström J. , Stolt L.
Published: July 2003

Thin films of Cu(In,Ga)Se2are grown by a co‐evaporation process in which the In, Ga, and Se fluxes, as well as the substrate temperature, are constant and the only variable is the Cu flux. This Cu flux varies in three steps in such a way that the growing film evolves from Cu‐poor to Cu‐rich and then back to Cu‐poor. The film growth is monitored by the ‘end point detection’ method, and film thicknesses of the order of 2 μm are deposited in less than 20 min. Quality devices (efficiencies above 15%) are produced in our baseline processes for all of the other synthesis steps. The Cu(In,Ga)Se2layers are studied from a (112) versus (220) (204) orientation and recrystallization point of view. Including the results from a previous study on the influence of the substrate temperature to the present X‐ray diffraction and scanning as well as tunneling electron microscopy data, a five‐stage growth model for the films is described. The specific features of these films are that they are weakly (220) (204) oriented and exhibit crevices in their top fractions. The growth model hypothesizes about the origins of these crevices and on how to avoid them. Copyright © 2003 John Wiley & Sons, Ltd.
General temperature dependence of solar cell performance and implications for device modelling
Authors: Green Martin A.
Published: July 2003

Solar cell performance generally decreases with increasing temperature, fundamentally owing to increased internal carrier recombination rates, caused by increased carrier concentrations. The temperature dependence of a general solar cell is investigated on the basis of internal device physics, producing general results for the temperature dependence of open‐circuit voltage and short‐circuit current, as well as recommendations for generic modelling. Copyright © 2003 John Wiley & Sons, Ltd.
Record efficiencies for EFG and string ribbon solar cells
Authors: Hahn G. , Geiger P.
Published: July 2003

Solar cells have been processed on Edge‐defined Film‐fed Growth and String Ribbon silicon. Based on a standard process developed for different types of multicrystalline materials including evaporation of contacts and photolithography for front‐contact formation, optimisations have been implemented to deal with the special needs of these low‐cost ribbon materials. Especially a remote plasma hydrogenation step and a change from evaporated to screen‐printed aluminium back‐surface‐field improved cell parameters drastically. Independently confirmed stable efficiencies of 16.7% (EFG) and 17.7% (String Ribbon) have been achieved on 4 cm2cells (full area). These values represent the highest stable efficiencies obtained for multicrystalline silicon ribbons so far. Copyright © 2003 John Wiley & Sons, Ltd.
Solar cell efficiency tables (version 22)
Authors: Green Martin A. , Emery Keith , King David L. , Igari Sanekazu , Warta Wilhelm
Published: July 2003

Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined and new entries since January 2003 are reviewed. Copyright © 2003 John Wiley & Sons, Ltd.
Familial aggregation of prostate cancer in African‐Americans and white Americans
Authors: Cunningham Glenn R. , Ashton Carol M. , Annegers John F. , Souchek Julianne , Klima Marcella , Miles Brian
Published: July 2003

BACKGROUND

We compared the incidence of prostate cancer in first‐degree family members of African‐Americans with that in white Americans.

METHODS

A historical cohort design was used to enroll 330 incident cases <80 years of age that were diagnosed at the Houston VA Medical Center between June 9, 1993 and June 8, 1996. We compared incidence rates in the probands' families with the incidence rates found in contemporaneous data from the national and regional Surveillance, Epidemiology, and End‐Results (SEER) program.

RESULTS

Three‐hundred five probands (41% African‐American) had evaluable first‐degree relatives (394 African‐American, 527 non‐African‐American). The standardized incidence ratio was 1.61 overall (95% confidence interval (CI): 1.22–2.13) and did not differ between African‐American and non‐African‐American families: 1.58 (1.05–2.29) and 1.65 (1.06–2.45) in African‐Americans and non‐African‐Americans, respectively.

CONCLUSIONS

The similar level of familial aggregation is evidence that the higher incidence of prostate cancer in African‐Americans is not attributable to a higher prevalence of germline mutations predisposing to the disease. Prostate 56: 256–262, 2003. © 2003 Wiley‐Liss, Inc.
Quantitative PSA RT‐PCR for preoperative staging of prostate cancer
Authors: Kurek Ralf , Ylikoski Alice , Renneberg Heiner , Konrad Lutz , Aumüller Gerd , Roddiger Sandra J. , Zamboglou Nikolaos , Tunn Ulf W. , Lilja Hans
Published: July 2003

BACKGROUND

The clinical value of detecting prostate specific antigen (PSA) mRNA in the peripheral blood mononuclear cell fraction of patients (pts) by standard RT‐PCR assays with localized prostate cancer remains controversial. We used a quantitative RT‐PCR assay to measure the PSA mRNA copy number in addition to the qualitative PSA RT‐PCR and correlated the results with clinical parameters.

METHODS

Total RNA was extracted from the peripheral blood mononuclear cell fraction of 115 prostate cancer pts prior to radical retropubic prostatectomy (RP) who received 3 months of neoadjuvant androgen deprivation. For quantitative RT‐PCR, a PSA‐like internal standard (IS) was added to each sample prior to reverse transcription and the PCR products for PSA and IS were selectively detected with fluorescent europium chelates after hybridization. Corresponding qualitative PSA–RT‐PCR was performed for all samples.

RESULTS

The median PSA copy number was 126 (range: 0–37988). There were no significant correlations established between qualitative or quantitative RT‐PCR results and given clinical parameters. Corresponding quantitative and qualitative RT‐PCR results were significantly associated (P = 0.01).

CONCLUSIONS

We were unable to show any additional value of quantitative as well as qualitative PSA RT‐PCR for preoperative staging of prostate cancer so far. Nevertheless, the long‐term follow up of the patients has to be awaited. Prostate 56: 263–269, 2003. © 2003 Wiley‐Liss, Inc.
Mitogen‐activated protein kinase pathway is involved in androgen‐independent PSA gene expression in LNCaP cells
Authors: Franco Omar E. , Onishi Takehisa , Yamakawa Kensuke , Arima Kiminobu , Yanagawa Makoto , Sugimura Yoshiki , Kawamura Juichi
Published: July 2003

BACKGROUND

Prostate specific antigen (PSA) is regulated by growth factors and hormones through functional androgen responsive elements in the promoter region of the PSA gene. However, the molecular basis for androgen independent PSA elevation in hormone refractory prostate cancer is unknown. The purpose of this study was to investigate the role of MAP kinase activation in androgen independent regulation of PSA expression.

METHODS

LNCaP cells transfected with MEK1 expression vector with or without the MAP kinase inhibitor U0126 under low androgen conditions were analyzed by luciferase assay and electrophoretic mobility shift assay (EMSA).

RESULTS

Transfection experiments of the proximal PSA promoter linked to Luc‐reporter identified one region designated as “B” motif centered at −60 bp to be essential for basal activation. Co‐transfection with the MEK1 activated vector enhanced PSA expression, while mutation of the “B” motif totally abrogated this induction. EMSA showed a specific DNA–protein complex, but Sp1 family members and AR do not interact with the “B” region by supershift analysis.

CONCLUSIONS

Our data suggest that enhanced androgen‐independent PSA gene expression in MAP kinase‐induced LNCaP cells is mediated, at least in part, by the “B” motif of the PSA promoter. Prostate 56: 319–325, 2003. © 2003 Wiley‐Liss, Inc.
Human prostate cancer cells and xenografts are targeted and destroyed through luteinizing hormone releasing hormone receptors
Authors: Leuschner Carola , Enright Frederick M. , Gawronska–Kozak Barbara , Hansel William
Published: July 2003

BACKGROUND

A conjugate of a lytic peptide, hecate, and a 15‐amino acid segment of the β‐chain of chorionic gonadotropin (CG) destroyed human prostate xenografts in nude mice by targeting LH receptors. Since these xenografts also express LHRH receptors, we prepared a LHRH–hecate conjugate and tested its ability to destroy PC‐3 cells in vitro and in vivo.

MATERIALS AND METHODS

LHRH–hecate was added to cultures of PC‐3, BRF 41 T, DU145, and LNCaP cells in the presence and absence of steroids. PC‐3 xenografts were established in nude male mice, which were treated with LHRH–hecate.

RESULTS

Injections of LHRH–hecate resulted in tumor growth arrest and marked reduction of tumor burden (62.2 mg/g body weight in saline controls vs. 10.5 mg/g body weight in treated mice;P < 0.0001); unconjugated LHRH and hecate had no effect on tumor burden and tumor viability (48.5 mg/g body weight in LHRH treated animals vs. 63.2 mg/g body weight in hecate treated mice). Marked tumor necrosis occurred in conjugate treated mice. Removal of steroids from the culture media decreased the sensitivity of LNCaP and PC‐3 cells to the LHRH–hecate; adding estrogen restored the sensitivity.

CONCLUSIONS

LHRH–hecate may be effective in treating hormone dependent and independent prostate cancers. Prostate 56: 239–249, 2003. © 2003 Wiley‐Liss, Inc.
Elevated serum progastrin‐releasing peptide (31–98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer
Authors: Yashi Masahiro , Nukui Akinori , Kurokawa Shinsuke , Ochi Masanori , Ishikawa Shinya , Goto Kentaro , Kobayashi Yutaka , Muraishi Osamu , Tokue Akihiko
Published: July 2003

BACKGROUND

The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen‐independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen‐deprived milieu in prostate cancer cells. On the basis that serum progastrin‐releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide.

METHODS

Serum ProGRP status was determined with an enzyme‐linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model.

RESULTS

The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen‐independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate‐specific antigen (PSA) levels were associated with a lower progression‐free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone‐related factors. Serum ProGRP was the most significant predictor among pre‐treatment factors in this model (P = 0.0094).

CONCLUSIONS

The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen‐independent disease progression. Prostate 56: 305–312, 2003. © 2003 Wiley‐Liss, Inc.
Stable expression of full length human androgen receptor in PC‐3 prostate cancer cells enhances sensitivity to retinoic acid but not to 1α,25‐dihydroxyvitamin D3
Authors: Murthy Shalini , Marcelli Marco , Weigel Nancy L.
Published: July 2003

BACKGROUND

PC‐3 prostate cancer cell growth is inhibited by 1α,25‐dihydroxyvitamin D3 (1,25 D) and retinoids, but not to the same extent as the androgen receptor (AR) positive LNCaP prostate cancer cells. Previous reports suggest a role for AR in growth inhibition of LNCaP cells by 1,25 D and retinoids. PC‐3 cells do not express AR. We therefore asked whether re‐expression of AR would enhance the response of PC‐3 cells to 1,25 D and retinoids.

METHODS

PC‐3 cells were stably transfected with wild type human AR cDNA. Pooled cells expressing AR protein at levels comparable to LNCaP cells were used to analyze response to 1,25 D, retinoids, androgens, and anti‐androgens.

RESULTS

AR re‐expression in PC‐3 cells restored response to androgens and anti‐androgens, but growth inhibition by 1,25 D was not significantly altered. However, cells were sensitized to low levels of retinoids, and, in contrast to the parental PC‐3 cells, sub‐optimal levels of 1,25 D and retinoids caused additive growth inhibition.

CONCLUSIONS

Restoring AR expression and activity in PC‐3 cells results in enhanced sensitivity to low levels of retinoids while the response to 1,25 D remains unaltered. Thus, the involvement of AR in prostate cancer growth inhibition by 1,25 D appears to be cell line specific. Prostate 56: 293–304, 2003. © 2003 Wiley‐Liss, Inc.
Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer
Authors: Miyoshi Yasuhide , Ishiguro Hitoshi , Uemura Hiroji , Fujinami Kiyoshi , Miyamoto Hiroshi , Miyoshi Yoshiko , Kitamura Hitoshi , Kubota Yoshinobu
Published: July 2003

BACKGROUND

Androgen receptor (AR) transcription is modulated by several cofactors such as AR associated proteins (ARA) including ARA70, ARA54, and ARA55. ARA55 increases AR transcription and alters ligand specificity. We hypothesized that ARA55 might play an important role in prostate cancer development or progression. We evaluated the messenger RNA (mRNA) expression of ARA55 in prostate cancer tissues, and analyzed the relation between ARA55 expression and clinical characteristics.

METHODS

A total of 30 prostate cancer specimens (20 previously untreated prostate cancers and 10 recurrent, hormone‐refractory prostate cancers (HRPC)) and 5 benign prostatic hypertrophy (BPH) tissue samples were examined. mRNA expression of ARA55 and AR were analyzed by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) using real time PCR.

RESULTS

ARA55 expression was identified in all tissue samples of previously untreated prostate cancer, HRPC and BPH. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer (P = 0.02) or BPH (P = 0.005) samples using quantitative PCR. On the other hand, higher ARA55 expression was associated with shorter recurrence‐free survival (P = 0.02) and overall survival (P = 0.01) in HRPC patients. AR expression was also revealed in all specimens of both prostate cancer and BPH. AR expression level in HRPC samples was significantly higher than that in previously untreated prostate cancer (P = 0.001) and BPH (P = 0.01) samples.

CONCLUSIONS

ARA55 may be associated with prostate cancer development and progression. ARA55 expression level in HRPC specimens was significantly lower than that in previously untreated prostate cancer or BPH specimens. On the contrary, our results suggested that a higher ARA55 expression level may result in unfavorable recurrence‐free survival and overall survival in HRPC patients. The role of ARA55 may differ between prostate cancer development and the process of progression to a hormone‐refractory state. These data not only help to understand the molecular mechanism of prostate cancer development or recurrence, but may also lead to a therapeutic strategy for recurrent prostate cancer that is refractory to hormonal treatment. Prostate 56: 280–286, 2003. © 2003 Wiley‐Liss, Inc.
Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues
Authors: Yousef George M. , Stephan Carsten , Scorilas Andreas , Ellatif Mohamed Abd , Jung Klaus , Kristiansen Glen , Jung Monika , Polymeris Mary‐Ellen , Diamandis Eleftherios P.
Published: July 2003

BACKGROUND

Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. KLK14 is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts.

METHODS

Matched prostate tissue samples from the cancerous and non‐cancerous parts of the same prostates were obtained from 100 patients who underwent radical prostatectomy. Quantitative analysis of KLK14 expression levels were performed by real‐time RT‐PCR using SYBR Green I dye on the LightCycler™ system. Associations with clinico‐pathological parameters were analyzed.

RESULTS

KLK14 overexpression in the cancerous compared to non‐cancerous tissue was found in 74% of patients (P < 0.001). Mean level of expression was 154 arbitrary units (Au) in cancerous tissues and 14.2 Au in the non‐cancerous tissues. The ratio of the cancerous to non‐cancerous KLK14 expression values was higher in patients with late stage (stage III) compared to stage II (P = 0.002), and in grade 3 compared to grade 1/2 tumors (P = 0.001). A statistically significant increase was also observed in patients with higher in Gleason score (>6) compared to Gleason score = 6 tumors (P = 0.027). No correlation was found between KLK14 tissue expression levels and serum prostate‐specific antigen.

CONCLUSIONS

KLK14 expression is significantly higher in cancerous compared to non‐cancerous prostatic tissue. The up‐regulation of the KLK14 gene in advanced and more aggressive tumors may indicate a possible role for the hK14 protein in tumor spread and opens the possibility of hK14 being a candidate new marker for prostate cancer diagnosis and prognosis. Prostate 56: 287–292, 2003. © 2003 Wiley‐Liss, Inc.
Interstitial cells in the human prostate: A new therapeutic target?
Authors: Aa Frank Van der , Roskams Tania , Blyweert Wim , Ridder Dirk De
Published: July 2003

BACKGROUND

Interstitial cells have been described in different human organs, including gut and bladder. In the gut they function as pacemaker cells, generating slow wave potentials. Absence or defects in these cells result in motility disorders. In the bladder these cells express the vanilloid receptor and may contribute to the working mechanism of vanilloid therapy. Recently, slow wave potentials and interstitial cells were described in the guinea‐pig prostate. In this study we describe the presence of interstitial cells in the human prostate gland.

METHODS

We performed immunohistochemical staining for c‐kit, vanilloid receptor (VR1), cannabinoid receptor (CB1) connexin43, and neurofilament on fresh frozen tissue from 14 prostatectomy specimens.

RESULTS

A large number of cells with a stellate aspect were noticed under the basal layer of the prostatic duct system and in between the smooth muscle cells. They were immunoreactive for c‐kit, VR1, and connexin43 but not to CB1 or neurofilament.

CONCLUSIONS

There is evidence for interstitial cells in the human prostate. Taken together their topography and immunohistochemical characterization, the discovery of slow wave potentials in guinea pig prostate and the knowledge of interstitial cells in other organs, interstitial cells are likely to be involved in normal prostate physiology. Prostate 56: 250–255, 2003. © 2003 Wiley‐Liss, Inc.
Identification of an HLA‐A*0201‐restricted T‐cell epitope derived from the prostate cancer‐associated protein trp‐p8
Authors: Kiessling Andrea , Füssel Susanne , Schmitz Marc , Stevanovic Stefan , Meye Axel , Weigle Bernd , Klenk Ulrich , Wirth Manfred P. , Rieber Ernst P.
Published: July 2003

BACKGROUND

New concepts for the immunotherapy of prostate carcinoma (PCa) largely depend on the identification of suitable target antigens that are present in a high percentage of prostate tumors. Their expression in normal tissues should be restricted to the prostate and they should be immunogenic in vivo. The number of antigens displaying these properties is still limited. Here, we identify for the first time an immunogenic peptide derived from the prostate‐specific protein transient receptor potential‐p8 (trp‐p8) that is recognized by cytotoxic T lymphocytes (CTLs) from PCa patients.

METHODS

To determine the abundance of trp‐p8 in prostate tumors, the expression level of trp‐p8 mRNA was quantitatively analyzed in a panel of prostate cancer tissues. Trp‐p8‐derived human leukocyte antigen (HLA)‐A*0201‐restricted peptides were selected and tested for the in vitro activation of CTLs when loaded on autologous dendritic cells (DCs).

RESULTS

Trp‐p8 mRNA was found to be expressed in all prostate tumors and in the corresponding normal prostate tissue. Of five selected trp‐p8‐derived peptides, only peptide GLMKYIGEV was shown to activate specific CTLs, which effectively lysed PCa cells confirming the endogenous generation and presentation of this peptide by tumor cells.

CONCLUSIONS

Our results suggest this antigen as a suitable target for the T‐cell‐based immunotherapy of PCa. Prostate 56: 270–279, 2003. © 2003 Wiley‐Liss, Inc.
Norepinephrine activates P44 and P42 MAPK in human prostate stromal and smooth muscle cells but not in epithelial cells
Authors: Kanagawa Kenji , Sugimura Kazunobu , Kuratsukuri Katsuyuki , Ikemoto Shin‐ichi , Kishimoto Taketoshi , Nakatani Tatsuya
Published: July 2003

BACKGROUND

In vascular smooth muscle cells, α1‐adrenergic stimulation increases DNA synthesis and cell proliferation via activation of p44/42 (ERK1/2) MAPK. We examined whether norepinephrine (NE) activates MAPK and stimulates the proliferation of prostatic epithelial and non‐epithelial cells.

METHODS

Human prostatic epithelial cells, stromal cells, and smooth muscle cells were purchased from BioWhittaker (Walkersville, MD). After reaching a semi‐confluent condition, the cells were cultured in RPMI‐1640 without serum for 1 day. At 10 min after adding NE (10−6 or 10−7 M) to the medium, the cells were collected. Cell lysate was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) followed by Western blot using anti‐phospho‐p44/42 and anti‐p44/42 antibodies. The activation of p44/42 was estimated by the ratio of phospho‐p44/42 to total p44/42. Cell proliferation was evaluated by 3H‐thymidine uptake assay. After reaching a semi‐confluent condition, the cells were cultured in RPMI‐1640 containing 0.5% FCS with or without NE (10−6 or 10−7 M) for 16 hr followed by a 3H‐thymidine uptake period (24 hr).

RESULTS

P44/42 MAPK was significantly activated by NE in non‐epithelial cells (stromal cells and smooth muscle cells) while not in epithelial cells. The uptake of 3H‐thymidine was significantly increased by NE in both non‐epithelial cells, which was inhibited by α1‐adrenoceptor antagonists.

CONCLUSIONS

These results suggest that NE may stimulate the proliferation of non‐epithelial prostatic cells, which may be involved in the pathogenesis of BPH. Prostate 56: 313–318, 2003. © 2003 Wiley‐Liss, Inc.
Strain effects on photoluminescence polarization of InAs/GaAs self‐assembled quantum dots
Authors: Jayavel P. , Tanaka H. , Kou K. , Kita T. , Wada O. , Ebe H. , Nakata Y. , Sugawara M.
Published: July 2003

We have investigated the photoluminescence (PL) polarization properties of InAs/GaAs self‐assembled quantum dots (QDs). An 8 nm InxGa1–xAs capping layer was overgrown on InAs QDs in order to modify the strain distribution in the dots. TE and TM mode PL polarizations of samples with capping layer indium composition of x = 0 and x = 0.13 were detected and analyzed. The TE/TM ratio shows heavy‐hole dominant optical transition for samples with x = 0. On the other hand, samples with x = 0.13 show light‐hole dominant optical transition. These results indicate valence band state inversion through in‐plane strain distribution dependent on the capping layer composition.
High‐quality InxGa1–xAs/Al0.30Ga0.70As quantum dots grown in inverted pyramids
Authors: Pelucchi E. , Baier M. , Ducommun Y. , Watanabe S. , Kapon E.
Published: July 2003

We report here on the fabrication by organometallic chemical vapour deposition of InxGa1–xAs quantum dots (QDs) with x up to 35% grown in pyramidal recess patterns with Al0.30Ga0.70As barriers. We show QD luminescence with narrow PL lines, tuning of the emission energies varying by more than 180 meV and ground state to first excited state separations as large as 80 meV.
Two‐dimensional ordering of InGaAs quantum dots formed on an artificial nano‐hole array with 100 nm periodicity
Authors: Nakamura Y. , Ikeda N. , Sugimoto Y. , Nakamura H. , Ohkouchi S. , Asakawa K.
Published: July 2003

We have successfully formed two‐dimensionally ordered InGaAs and InAs quantum dots (QDs) by controlling the nucleation sites on artificially prepared nano‐hole arrays with a 100 nm periodicity. The ordered InGaAs QDs were realized by a combination of a low‐temperature deposition of InGaAs and its annealing on the nano‐hole arrays. These ordered InGaAs played a role as a template for upper InAs QDs. In this study, we used in situ scanning tunneling microscopy (STM), which enabled us to observe each grown surface on the samples.
Theory of optical manipulation of semiconductor quantum dots confining excitons
Authors: Iida T. , Ishihara H.
Published: July 2003

We present a theoretical study of optical manipulation of spherical semiconductor quantum dots confining excitonic center‐of‐mass motion. The radiation force that is exerted on a dot floating in a vacuum is calculated by using the Maxwell stress tensor expressed in terms of the microscopic response field. The following advantageous effects are clarified: (1) The acceleration (the force normalized by the mass of a dot) exerted by the resonant light is greatly enhanced for a dot with a radius of less than 100 nm. Especially, for smaller dots with a radius near 10 nm, this enhancement is conspicuous. (2) The spectral peak position of exerted force is extremely sensitive to nanoscale‐size changes, which can be utilized for size selection of quantum dots. Such results will open the way to the fabrication of nanostructures composed of arranged quantum dots with ultrahigh homogeneity.
Designing quantum systems in self‐assembled quantum dots
Authors: Korkusinski M. , Sheng W. , Hawrylak P.
Published: July 2003

The possibility of designing electronic properties of quantum dots by varying shell spacing, number of confined shells, and number of electrons is investigated. Numerical results demonstrate the creation of magnetic moments beyond Hunds rules.
Optical spin polarization in negatively charged InAs self‐assembled quantum dots under applied electric field
Authors: Kalevich V. K. , Ikezawa M. , Okuno T. , Shiryaev A. Yu. , Zhukov A. E. , Ustinov V. M. , Brunkov P. N. , Masumoto Y.
Published: July 2003

We have studied the influence of an external electric field on the optical spin polarization of initially negatively charged InAs/GaAs quantum dots (QDs). The spin polarization of the carriers was controlled by measuring the photoluminescence (PL) circular polarization. We have found that the PL polarization of the QD is negative under an excitation above the GaAs barrier, and that it becomes positive under an excitation below the barrier. An applied negative electric field destroys both positive and negative polariza‐tion. The time decay of the negative polarization was found from time‐resolved measurements to exceed strongly the QD radiative lifetime. This fact indicates a long‐living spin memory in the dots under study.
Polaron relaxation in InAs/GaAs self‐assembled quantum dots
Authors: Sauvage S. , Boucaud P. , Bras F. , Fishman G. , Lobo R. P. S. M. , Glotin F. , Prazeres R. , Ortega J.‐M. , Gérard J.‐M.
Published: July 2003

Polaron dynamics in n‐doped InAs/GaAs self‐assembled quantum dots is investigated using far infrared pump–probe spectroscopy around 22 μm wavelength of the s–p intersublevel transition. Despite the strong coupling between the confined electron and the phonon continuum, forming a priori an everlasting polaron, we show experimentally that the polaron actually relaxes over a tens‐of‐picoseconds time range even at detuning far away from the phonon resonance. Measured decay times scale from 45 ps to 70 ps at low temperature depending on the transition energy. The energy dependence of this relaxation time is consistent with the polaron nature of the elementary excitation in InAs/GaAs self‐assembled quantum dots. As the temperature increases, the polaron decay time slightly decreases, with still a value of 37 ps at 300 K. The experiment shows that the polaron relaxation is driven by the instability of its one‐phonon component. It is consistent with a phonon part disintegrating into two acoustic phonons as proposed theoretically by Li, Nakayama and Arakawa in 1999 [4].
Hole storage in GaSb/GaAs quantum dots for memory devices
Authors: Geller M. , Kapteyn C. , Müller‐Kirsch L. , Heitz R. , Bimberg D.
Published: July 2003

The hole confinement of self‐organized GaSb/GaAs quantum dots embedded in n+p‐diodes is investigated experimentally by admittance spectroscopy. The highest thermal activation energy obtained, 400 meV, refers to only weakly charged quantum dots. Detailed bias‐dependent investigations allow to study state‐ filling and Coulomb charging effects. State filling lowers the activation energy down to 150 meV in quantum dots charged with the maximum number of about 15 holes. The observed thermal activation barrier for GaSb/GaAs quantum dots is about twice as high as for structurally comparable InAs/GaAs quantum dots.
Investigation of spin state in a quantum dot by using strongly asymmetric tunnel barriers
Authors: Hayashi T. , Fujisawa T. , Hirayama Y.
Published: July 2003

We investigate the spin state of a GaAs lateral quantum dot (QD) by using strongly asymmetric tunnel barriers. The saturated current depends on the current polarity, which switches the direction of the dominant tunneling transition that increases or decreases the total spin. With this technique, the spin polarization and the Coulomb interaction are investigated. We find that high spin states appearing in some magnetic field regions can be understood by considering simple Coulomb interactions.
Polarized electrons, trions, and nuclei in charged quantum dots
Authors: Bracker A. S. , Tischler J. G. , Korenev V. L. , Gammon D.
Published: July 2003

We have investigated spin polarization in GaAs quantum dots. Excitons and trions are polarized directly by optical excitation and studied through polarization of photoluminescence. Electrons and nuclei are polarized indirectly through subsequent relaxation processes. Polarized electrons are identified by the Hanle effect for exciton and trion photoluminescence, while polarized nuclei are identified through the Overhauser effect in individual charged quantum dots.
Shape‐dependent properties of self‐organized quantum dots: Few‐particle states and exciton‐phonon coupling
Authors: Heitz R. , Rodt S. , Schliwa A. , Bimberg D.
Published: July 2003

The electronic and optical properties of self‐organized InAs/GaAs quantum dots are investigated in view of the actual structural properties. Focussing on the shape we demonstrate theoretically a strong impact of the varying strain distribution on the electronic and, in particular, the exciton properites in such quantum dots. The inhomogeneous strain, typical for self‐organized quantum dots, lowers the symmetry and increases the local charge density. Resonant Raman experiments on pyramidal InAs/GaAs quantum dots show an enhance exciton–LO‐phonon coupling reflecting the strain‐induced local charge density. Experiments on single InAs/GaAs quantum dots demonstrate an unexpected strong impact of the structural properties on few‐particle complexes on the example of the biexciton complex. Anti‐binding biexciton complexes are demonstrated. The apparent correlation of the biexciton binding energy and exciton transition energy, with a transition from binding to anti‐binding at ∼1.24 eV, is attributed to a decreasing exciton localization, resulting from the finite barrier height. The Coulomb interaction with delocalized states is negligible for the energy of the localized states.
Magneto‐photoluminescence studies of a novel quantum dot–quantum well coupled system
Authors: Child R. A. , Nicholas R. J. , Mason N. J.
Published: July 2003

We report a study of novel structures in which an InSb quantum dot (QD) layer in GaSb is coupled to a nearby narrow InAs quantum well (QW). Magnetic fields have been used to probe the photoluminescence (PL) of the dots and the wells separately and in the coupled structures. We have found that the introduction of the dot–well coupling leads to a dramatic suppression of the diamagnetic shift of the exciton when the magnetic field is oriented parallel to the well plane. The observed shift is 1–2 meV with an applied field of 17 T. In contrast, when the field is perpendicular to the layer plane, there is little difference in the response of the coupled structures compared to that of the quantum wells on their own, suggesting that the behaviour is dominated by the motion of the electrons in the wells.
Real‐space mapping of exciton wave function in a GaAs quantum dot by near‐field optical imaging spectroscopy
Authors: Matsuda Kazunari , Saiki Toshiharu , Nomura Shintaro , Mihara Masaru , Aoyagi Yoshinobu
Published: July 2003

We describe near‐field photoluminescence imaging spectroscopy of a single naturally occurring GaAs quantum dot in a narrow quantum well. A spatial mapping of the center‐of‐mass wave function of the exciton state in the quantum dot is demonstrated due to the realization of a high spatial resolution (30 nm) of imaging spectroscopy and the selection of a large quantum dot (100 nm). We observe an elongation along the [110] crystal axis of the wave function in the exciton state.