bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comprehensive Strategy to Combat Colon Cancer Targeting the Adenomatous Polyposis Coli Tumor Suppressor Gene
Authors: GERNER EUGENE W. , IGNATENKO NATALIA A. , LANCE PETER , HURLEY LAURENCE H.
Published: December 2005

Abstract: Somatic cells in the majority of colorectal polyps and cancers contain mutations/deletions in the adenomatous polyposis coli (APC) tumor suppressor gene. APC is involved in normal intestinal development and acts to influence a variety of cellular processes. Loss of APC function leads to intestinal neoplasia in both mice and humans. APC influences expression of specific genes, including the c‐Myc oncogene, which functions as a transcriptional activator. Loss of APC function leads to alterations in c‐Myc‐regulated genes including ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis. A single nucleotide polymorphism (SNP) in the ODC promoter affecting c‐Myc‐dependent expression has been associated with risk of colorectal and other cancers. Pharmaceuticals that target structural features of the c‐Myc promoter, and suppress expression of c‐Myc and other genes regulated by similar promoter elements, are being developed as potential colorectal cancer chemotherapies. Difluoromethylornithine (DFMO), a selective inhibitor of ODC, is under clinical evaluation as a colorectal cancer chemopreventive agent. APC and APC‐dependent genes, such as c‐Myc and ODC, may be useful as genetic markers of risk and as targets for chemoprevention and therapy for colorectal cancer.
External Imaging of CCND1, MYC, and KRAS Oncogene mRNAs with Tumor‐Targeted Radionuclide‐PNA‐Peptide Chimeras
Authors: TIAN XIAOBING , CHAKRABARTI ATIS , AMIRKHANOV NARIMAN V. , ARUVA MOHAN R. , ZHANG KAIJUN , MATHEW BOBY , CARDI CHRISTOPHER , QIN WENYI , SAUTER EDWARD R. , THAKUR MATHEW L. , WICKSTROM ERIC
Published: December 2005

Abstract: In 2005, breast cancer will kill approximately 40,410 women in the U.S., and pancreatic cancer will kill approximately 31,800 men and women in the U.S. Clinical examination and mammography, the currently accepted breast cancer screening methods, miss almost half of breast cancers in women younger than 40 years, approximately one‐quarter of cancers in women aged 40‐49 years, and one‐fifth of cancers in women over 50 years old. Pancreatic cancer progresses rapidly, with only 1% of patients surviving more than 5 years after diagnosis. However, if the disease is diagnosed when it is localized, the 5‐year survival is approximately 20%. It would be beneficial to detect breast cancer and pancreatic cancer at the earliest possible stage, when multimodal therapy with surgery, radiotherapy, and chemotherapy have the greatest chance of prolonging survival. Human estrogen receptor‐positive breast cancer cells typically display elevated levels of Myc protein due to overexpression of MYC mRNA, elevated cyclin D1 protein due to overexpression of CCND1 mRNA, and elevated insulin‐like growth factor 1 receptor (IGF1R) due to overexpression of IGF1R mRNA. We hypothesized that scintigraphic detection of MYC or CCND1 peptide nucleic acid (PNA) probes with an IGF1 peptide loop on the C‐terminus, and a Tc‐99m‐chelator peptide on the N‐terminus, could measure levels of MYC or CCND1 mRNA noninvasively in human IGF1R‐overexpressing MCF7 breast cancer xenografts in immunocompromised mice. Similarly, human pancreatic cancer cells typically display elevated levels of KRAS mRNA and elevated IGF1R. Hence, we also hypothesized that a KRAS Tc‐99m‐chelator PNA‐peptide probe could detect overexpression of KRAS mRNA in pancreatic cancer xenografts by scintigraphic imaging, or by positron emission tomography (PET) with a KRAS Cu‐64‐chelator PNA‐peptide. Human MCF7 breast cancer xenografts in immunocompromised mice were imaged scintigraphically 4‐24 h after tail‐vein administration of MYC or CCND1 Tc‐99m‐chelator PNA‐peptides, but not after administration of mismatch controls. Similarly, human Panc‐1 pancreatic cancer cells xenografts were imaged scintigraphically 4 and 24 h after tail‐vein administration of a KRAS Tc‐99m‐chelator PNA‐peptide, and AsPC1 xenografts were imaged by PET 4 and 24 h after tail‐vein adminstration of a KRAS Cu‐64‐chelator PNA‐peptide. The radioprobes distributed normally to the kidneys, livers, tumors, and other tissues. External molecular imaging of oncogene mRNAs in solid tumors with radiolabel‐PNA‐peptide chimeras might in the future provide additional genetic characterization of pre‐invasive and invasive breast cancers.
Regulation of Cancer Cell Survival by Par‐4
Authors: RANGANATHAN PADHMA , RANGNEKAR VIVEK M.
Published: December 2005

Abstract: Prostate apoptosis response‐4 (Par‐4) is a unique pro‐apoptotic protein that selectively induces apoptosis in cancer cells. Moreover, Par‐4 sensitizes cells to the action of diverse apoptotic stimuli and causes tumor regression. This review discusses the prominent structural and functional features of Par‐4 and the multiple levels of regulation of its apoptotic function, all of which can be utilized to develop targeted cancer therapy.
Functional Validation of Genes Implicated in Lymphomagenesis: An in Vivo Selection Assay Using a Myc‐Induced B‐Cell Tumor
Authors: YU DUONAN , COZMA DIANA , PARK ANDREA , THOMAS‐TIKHONENKO ANDREI
Published: December 2005

Abstract: The involvement of the c‐Myc transcription factor in neoplastic transformation is well documented. However, which of its numerous target genes are crucial for tumorigenesis remains a frequently contested issue. We have recently established a non‐transgenic murine model for B‐cell lymphoma based on neoplastic conversion of p53‐null bone marrow cells by conditionally active Myc. Using this model, we have identified a number of genes whose expression levels are affected by Myc during B‐lymphomagenesis. Here we discuss their possible roles in neoplastic processes and describe an experimental approach allowing in vivo validation of these roles. We demonstrate that lymphoma cells overexpressing one of the Myc targets, the interleukin‐10 receptor gene, have a very strong selective advantage over low IL10R expressors. Furthermore, Mcl1, a presumptive IL10R effector, also confers selective advantages when overexpressed in Myc‐transformed hematopoietic cells. Thus, both IL10R and Mcl1 might be amenable to therapeutic interventions, and new targets can be identified and validated using the selection approach.
Comparison of CA-125 and Standard Definitions of Progression of Ovarian Cancer in the Intergroup Trial of Cisplatin and Paclitaxel Versus Cisplatin and Cyclophosphamide
Authors: Rustin Gordon J.S. , Timmers Petra , Nelstrop Ann , Shreeves Gavin , Bentzen Soeren M. , Baron Benoit , Piccart Martine J. , Bertelsen Kamma , Stuart Gavin , Cassidy James , Eisenhauer Elizabeth
Published: December 2005

Purpose

A definition for progression of ovarian cancer has been proposed based on either a confirmed doubling of CA-125 levels from the upper limit of normal or from the nadir level if levels are persistently elevated. Retrospectively, we determined whether the use of this CA-125 definition in a randomized trial would have shown the same magnitude of difference between the treatment arms as was shown when the standard progression definition was used.

Patients and Methods

A retrospective analysis was performed on 680 patients in the Taxol Intergroup Trial with advanced epithelial ovarian carcinoma, of whom 628 were assessable according to CA-125. The date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-125.

Results

Of the 628 patients assessable for both definitions, 556 clinical or radiologic progressions were determined compared with 389 according to the CA-125 definition. There was a highly significant difference in the hazard of progression between the paclitaxel and cisplatin arm (TP) compared with the cyclophosphamide and cisplatin arm (CP) when either standard or CA-125 criteria were used to define progression (standard, P = .002; CA-125, P = .011). The hazard ratio of TP/CP over time was similar when comparing the different methods of defining progression.

Conclusion

The results of this analysis show that the magnitude of the therapeutic benefit was similar whether CA-125 or standard criteria were used to define progression.
First-Line Single Agent Treatment With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer: A Phase II Study
Authors: Niho Seiji , Kubota Kaoru , Goto Koichi , Yoh Kiyotaka , Ohmatsu Hironobu , Kakinuma Ryutaro , Saijo Nagahiro , Nishiwaki Yutaka
Published: December 2005

Purpose

We conducted a phase II study of single agent treatment with gefitinib in chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC) to assess its efficacy and toxicity.

Patients and Methods

Patients received 250 mg doses of gefitinib daily. Administration of gefitinib was terminated if partial response (PR) was not achieved within 8 weeks or if tumor reduction was not observed within 4 weeks. In these cases, platinum-based doublet chemotherapy was given as a salvage treatment. We evaluated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples.

Results

Forty-two patients were enrolled between March and November 2003, with 40 of these patients being eligible. The response rate was 30% (95% CI, 17% to 47%). The most common toxicity included grade 1 or 2 acne-like rash (50%) and grade 1 diarrhea (18%). Grade 2 or 3 hepatic toxicity was observed in 8% of patients. Four patients developed grade 5 interstitial lung disease (ILD). Thirty patients received second-line chemotherapy. Median survival time was 13.9 months (95% CI, 9.1 to 18.7 months), and the 1-year survival rate was 55%. Tumor samples were available in 13 patients, including four cases of PR, six cases of stable disease, and three cases of progressive disease. EGFR mutations (deletions in exon 19 or point mutations [L858R or E746V]) were detected in four tumor tissues. All four patients with EGFR mutation achieved PR with gefitinib treatment.

Conclusion

Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC, but produces unacceptably frequent ILD in the Japanese population.
Preoperative Serum Tissue Factor Levels Are an Independent Prognostic Factor in Patients With Ovarian Carcinoma
Authors: Han Liz Y. , Landen Charles N. , Kamat Aparna A. , Lopez Adriana , Bender David P. , Mueller Peter , Schmandt Rosemarie , Gershenson David M. , Sood Anil K.
Published: December 2005

Purpose

Tissue factor (TF) is a procoagulant that plays an important part in tumor angiogenesis. We sought to determine the role of preoperative serum TF levels in predicting clinical outcome in patients with ovarian cancer.

Materials and Methods

TF expression was determined by reverse transcriptase polymerase chain reaction in ovarian cell lines. Using enzyme-linked immunosorbent assay, we assessed preoperative serum TF levels in 98 women with invasive epithelial ovarian carcinoma, 30 with low malignant potential (LMP) tumors, 16 with benign tumors, and a separate validation group of 39 women with adnexal masses. Clinical information was gathered from chart review.

Results

TF was expressed in four of the five ovarian cancer cell lines, but absent in the nontransformed cells. Ovarian cancer patients had a median preoperative serum TF level of 85.2 pg/mL, which was significantly higher than in those with LMP tumors (12.8 pg/mL; P < .01) and benign adnexal disease (30.7 pg/mL; P < .01). TF ≥ 190 pg/mL was significantly associated with decreased patient survival (P < .01). After adjusting for other clinical variables in a multivariate Cox regression model, TF ≥ 190 pg/mL was an independent prognostic factor (P < .01). Analysis of serum TF levels from the validation set confirmed that high TF (≥190 pg/mL) was associated with a 3.4-fold increase in risk of death from disease (P = .02) and shorter survival (P = .01).

Conclusion

Preoperative serum TF levels are significantly elevated in patients with ovarian carcinoma. Elevated preoperative TF level is an independent prognostic factor for death from disease.
Early Identification of Resistance to First-Line Single-Agent Methotrexate in Patients With Persistent Trophoblastic Disease
Authors: van Trommel Nienke E. , Massuger Leon F. , Schijf Charles P. , ten Kate-Booij Marianne J. , Sweep Fred C. , Thomas Chris M.
Published: December 2005

Purpose

A generally accepted definition for resistance to first-line single-agent chemotherapy for persistent trophoblastic disease (PTD) is lacking. In the present study, a normogram for serum human chorionic gonadotropin (hCG) from patients with normalization of serum hCG after first-line single-agent chemotherapy for PTD was constructed to identify patients resistant to this chemotherapy.

Patients and Methods

Between 1987 and 2004, data from 2,132 patients were registered at the Dutch Central Registry for Hydatidiform Moles. A normal serum hCG regression corridor was constructed for 79 patients with low-risk PTD who were cured by single-agent methotrexate (MTX) chemotherapy (control group). Another group of 29 patients with low-risk PTD needed additional alternative therapies (dactinomycin and multiagent chemotherapy) for failure of serum hCG to normalize with single-agent chemotherapy (study group).

Results

Serum hCG measurement preceding the fourth and sixth single-agent chemotherapy course proved to have excellent diagnostic accuracy for identifying resistance to single-agent chemotherapy, with an area under the curve (AUC) for receiver operating characteristic curve analysis of 0.949 and 0.975, respectively. At 97.5% specificity, serum hCG measurements after 7 weeks showed 50% sensitivity.

Conclusion

In the largest study to date, we describe the regression of serum hCG levels in patients with low-risk PTD successfully treated with MTX. At high specificity, hCG levels in the first few courses of MTX can identify half the number of patients who are extremely likely to need alternative chemotherapy to cure their disease and for whom further treatment with single-agent chemotherapy will be ineffective.
Low Value of [18F]-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography in Primary Staging of Early-Stage Cervical Cancer Before Radical Hysterectomy
Authors: Chou Hung-Hsueh , Chang Ting-Chang , Yen Tzu-Chen , Ng Koon-Kwan , Hsueh Swei , Ma Shih-Ya , Chang Chee-Jen , Huang Huei-Jean , Chao Angel , Wu Tzu-I , Jung Shih-Ming , Wu Yen-Ching , Lin Cheng-Tao , Huang Kuan-Gen , Lai Chyong-Huey
Published: December 2005

Purpose

The role of positron emission tomography (PET) with [18F]-fluoro-2-deoxy-d-glucose (FDG) in early-stage cervical cancer is unclear. We aimed to investigate the clinical benefit of FDG-PET in primary staging before radical hysterectomy and pelvic lymphadenectomy (RH-PLND).

Patients and Methods

Patients with untreated stage IA2 to IIA adenocarcinoma (AD) or adenosquamous carcinoma (ASC) or nonbulky (≤ 4 cm) squamous cell carcinoma cervical cancer with magnetic resonance imaging (MRI) –defined negative nodal metastasis were enrolled onto a prospective study with a two-stage design. All patients had a preoperative dual-phase FDG-PET, technetium-99m–sulfur colloid lymphoscintigraphy, and intraoperative sentinel lymph node (LN) detection at RH-PLND. The gold standard of LN metastasis is histologic. A sample size of 120 patients was calculated to fit study aims (diagnostic efficacy of PET and sentinel LN sampling). An interim analysis was performed when 60 patients were accrued, which led to the current report.

Results

There were 36 SCCs, 20 ADs, and four ASCs. Of the 60 patients, 10 (16.7%) had pelvic LN metastases, and one (1.7%) had para-aortic LN (PALN) metastasis histologically. FDG-PET detected the single PALN metastasis (one of one patient) but detected only one (10%) of the 10 pelvic LN metastases. The PET false-negative pelvic LN micrometastases measured a median of 4.0 × 3.0 mm (range, 0.5 × 0.5 to 7 × 6 mm). The second stage of this trial will be continued without PET.

Conclusion

This study shows that dual-phase FDG-PET has little value in primary, nonbulky, stage IA2 to IIA and MRI-defined, LN-negative cervical cancer.
Outcome of Critically Ill Allogeneic Hematopoietic Stem-Cell Transplantation Recipients: A Reappraisal of Indications for Organ Failure Supports
Authors: Pène Frédéric , Aubron Cécile , Azoulay Elie , Blot François , Thiéry Guillaume , Raynard Bruno , Schlemmer Benoît , Nitenberg Gérard , Buzyn Agnès , Arnaud Philippe , Socié Gérard , Mira Jean-Paul
Published: December 2005

Purpose

Because the overall outcome of critically ill hematologic patients has improved, we evaluated the short-term and long-term outcomes of the poor risk subgroup of allogeneic hematopoietic stem-cell transplantation (HSCT) recipients requiring admission to the intensive care unit (ICU).

Patients and Methods

This was a retrospective multicenter study of allogeneic HSCT recipients admitted to the ICU between 1997 and 2003.

Results

Two hundred nine critically ill allogeneic HSCT recipients were included in the study. Admission in the ICU occurred during the engraftment period (≤ 30 days after transplantation) for 70 of the patients and after the engraftment period for 139 patients. The overall in-ICU, in-hospital, 6-month, and 1-year survival rates were 48.3%, 32.5%, 27.2%, and 21%, respectively. Mechanical ventilation was required in 122 patients and led to a dramatic decrease in survival rates, resulting in in-ICU, in-hospital, 6-month, and 1-year survival rates of 18%, 15.6%, 14%, and 10.6%, respectively. Mechanical ventilation, elevated bilirubin level, and corticosteroid treatment for the indication of active graft-versus-host disease (GVHD) were independent predictors of death in the whole cohort. In the subgroup of patients requiring mechanical ventilation, associated organ failures, such as shock and liver dysfunction, were independent predictors of death. ICU admission during engraftment period was associated with acceptable outcome in mechanically ventilated patients, whereas patients with late complications of HSCT in the setting of active GVHD had a poor outcome.

Conclusion

Extensive unlimited intensive care support is justified for allogeneic HSCT recipients with complications occurring during the engraftment period. Conversely, initiation or maintenance of mechanical ventilation is questionable in the setting of active GVHD.
Psychological Distress in Men With Breast Cancer
Authors: Brain Kate , Williams Buddug , Iredale Rachel , France Liz , Gray Jonathon
Published: December 2005

Purpose

This article reports the first United Kingdom study to examine the prevalence of psychological distress in men with breast cancer and the factors associated with increased distress.

Patients and Methods

One hundred and sixty-one men with breast cancer completed a cross-sectional questionnaire that included measures of anxiety and depressive symptoms, cancer-specific distress, body image, coping, information and support needs, and clinical and demographic variables.

Results

Clinical levels of anxiety and depressive symptoms were reported by 6% and 1% of men, respectively, while 23% reported high levels of cancer-specific distress. Anxiety was most strongly associated with avoidance coping and fear and uncertainty about the future (42% of the variance in anxiety scores, P < .001). Depressive symptoms were associated with altered body image (35% of the variance, P < .001). Body image, avoidance coping, referral to the study by a clinician, fear and uncertainty, and wanting to receive more gender-specific information together explained 51% of the variance in cancer-related distress (P < .001). Clinical and demographic factors did not account for a significant proportion of the variance in any of the distress measures.

Conclusion

Although the prevalence of clinical anxiety and depressive symptoms were low in this sample, almost a quarter of men experienced traumatic stress symptoms specific to breast cancer. Potential risk factors for distress include the use of avoidant coping strategies, negative body image, feelings of fear and uncertainty in relation to breast cancer, and unmet information needs. Suggestions are made for improving the information and support available to men with breast cancer.
Minireview: Timely Ovulation: Circadian Regulation of the Female Hypothalamo-Pituitary-Gonadal Axis
Authors: de la Iglesia Horacio O. , Schwartz William J.
Published: December 2005

The preovulatory surge in the secretion of LH is timed by a neuroendocrine integrative mechanism that involves ovarian estradiol levels and the endogenous circadian system. Studies in female rats and hamsters have established that the clock in the hypothalamic suprachiasmatic nucleus has a preeminent role in setting the LH surge, and anatomical, physiological, and pharmacological data are revealing the responsible connections between suprachiasmatic nucleus neurons and GnRH and estradiol-receptive areas. Recent investigations show that GnRH and pituitary cells express circadian clock genes that might play a role in the release and reception of the GnRH signal. Analysis of the circadian regulation of the LH surge may provide a model for understanding how multiple neural oscillators function within other neuroendocrine axes.
A Minimal Controller Synthesis Algorithm for Narrow-Band Applications
Authors: Hillis A J , Neild S A , Stoten D P , Harrison A J L
Published: December 2005

A common control problem is that of reducing a narrow-band error signal or a narrow-band component of a broad-band error signal. The particular application described in this paper is that of active vibration isolation for automotive vehicles. The error-driven minimal control synthesis (Er-MCSI) algorithm with integral action has been applied to this problem, but is known to exhibit gain windup. The nature of the gain windup phenomenon is investigated and methods to mitigate its effects are discussed. A new controller, the narrow-band MCS (NBMCS), is developed specifically for narrow-band applications. NBMCS is based upon Er-MCSI and exploits the deterministic nature of the system disturbance. The NBMCS algorithm is shown not to suffer from the gain windup problem. The properties and performance of the Er-MCSI and NBMCS controllers are compared analytically, via simulation and experimental application, to an automotive vehicle equipped with active engine mounts.
Chiral Symmetry Breaking in Chiral Crystallization and Soai Autocatalytic Reaction
Authors: Gridnev Ilya D
Published: December 2005

Complete chiral crystallization and absolute chiral synthesis are both fascinating phenomena shedding light on the possible origins of homochirality in nature and opening perspectives for efficient preparations of optically pure materials. Originally these two phenomena have been considered mechanistically quite different belonging to the hetero- and homogeneous systems, respectively. However, the results of the active research in both fields undertaken in the last few years suggest that there may be a much closer likeness of the most important mechanistic features of these two phenomena. In the present review, we bring together the latest data on the complete chiral crystallization and absolute chiral synthesis including our own data on the mechanism and spontaneous break of chirality in the Soai asymmetric autocatalysis.
Evidence of reciprocal tertiary interactions between conserved motifs involved in organizing RNA structure essential for internal initiation of translation
Authors: FERNÁNDEZ-MIRAGALL OLGA , RAMOS RICARDO , RAMAJO JORGE , MARTÍNEZ-SALAS ENCARNACIÓN
Published: December 2005

Internal ribosome entry site (IRES) elements consist of highly structured RNA regions that determine internal initiation of translation. We have previously shown that the foot-and-mouth disease virus (FMDV) IRES contains a GNRA tetraloop spanning residues G178UAA181. Here we show that tertiary RNA interactions dependent on the GNRA motif determine the structural organization of the central domain. By using mutational analysis in combination with RNA probing, we have identified distant reciprocal interactions between the GNRA motif and the invariant region G240CACG244, termed motif A. Mutations in motif A caused a decrease in IRES activity as severe as the GUAG substitution in the GNRA motif. Substitutions in either GNRA or motif A sequences induced a common reorganization around the conserved R199AAA202 stem–loop, suggesting that the latter contributes to stabilize the GNRA–motif A interaction. This finding was also consistent with a significant increase in the efficiency of RNA–RNA interactions determined in gel shift assays using as probe the hairpin that contains the GNRA motif compared to a transcript encompassing the entire apical region of the central domain. Thus, we propose that the central domain of the FMDV IRES contains a structural conformation essential for IRES activity stabilized by a tertiary contact involving residues in the GNRA tetraloop and motif A conserved sequences.
Prp8p dissection reveals domain structure and protein interaction sites
Authors: BOON KUM-LOONG , NORMAN CHRISTINE M. , GRAINGER RICHARD J. , NEWMAN ANDREW J. , BEGGS JEAN D.
Published: December 2005

We describe a novel approach to characterize the functional domains of a protein in vivo. This involves the use of a custom-built Tn5-based transposon that causes the expression of a target gene as two contiguous polypeptides. When used as a genetic screen to dissect the budding yeast PRP8 gene, this showed that Prp8 protein could be dissected into three distinct pairs of functional polypeptides. Thus, four functional domains can be defined in the 2413-residue Prp8 protein, with boundaries in the regions of amino acids 394–443, 770, and 2170–2179. The central region of the protein was resistant to dissection by this approach, suggesting that it represents one large functional unit. The dissected constructs allowed investigation of factors that associate strongly with the N- or the C-terminal Prp8 protein fragments. Thus, the U5 snRNP protein Snu114p associates with Prp8p in the region 437–770, whereas fragmenting Prp8p at residue 2173 destabilizes its association with Aar2p.
The Effect of Aggregate Gradation on Engineering Properties of High Performance Concrete
Authors: Tasi CT , Li LS , Hwang CL
Published: December 2005

The main theme of this paper is to study the effects of aggregate packing types on the engineering properties of high performance concrete (HPC). Three types of aggregate packing (primitive, dense, gap gradation) and five kinds of paste amount (1.2, 1.4, 1.6, 1.8, 2.0 of void content within aggregate) are the major parameters to evaluate the properties of HPC. The test result indicates that the denser the aggregate packing the better the workability and engineering properties are under sufficient paste content. The application of the densified mixture design algorithm (DMDA) on designing HPC for every aggregate packing type can obtain high flowability and suitable strength growth. The strength efficiency of HPC designed by DMDA is much higher than that by the traditional one. The significant contribution of the aggregate packing to the performance of hardened HPC is obvious. The conclusion is that by applying DMDA, the gap-graded aggregate or other marginal material may be utilized to produce HPC.
Benchmark on the 3-D VENUS-2 MOX-Fueled Reactor Dosimetry Calculations by DANTSYS Code System
Authors: Kim DH , Gil C-S , Chang J
Published: December 2005

The benchmark calculation for the 3-D VENUS-2 MOX-fueled reactor dosimetry has been performed by the TRANSX/DANTSYS code system. The nuclear data from the ENDF/B-VI.8, JENDL-3.3, and JEFF-3.0 have been processed for the MATXS-format 199-group neutron libraries by NJOY99.90. The equivalent fission fluxes at the 34 measurement positions on the core mid-plane have been calculated using the dosimetry reaction rates for the 58Ni(n,p), 115In(n,n'), 103Rh(n,n'), 64Zn(n,p), 237Np(n,f), and 27Al(n,α) detectors. The estimated results by the JENDL-3.3 and JEFF-3.0 have been compared with those by the ENDF/B-VI.8.
Dosimetry Requirements for Pressure Vessel Steels Toughness Curve in the Ductile to Brittle Range
Authors: Carcreff H , Alberman A , Barbot L , Rozenblum F , Beretz D , Lee YK
Published: December 2005

As part of PWR life-time assessment project, a large R&D program, PV-CT50, has been carried out from 1995 to 2004, to assess pressure vessel (PV) steel's toughness curve using very large compact tension (CT) specimens (50 × 125 × 120 mm3) allowing measurements in the ductile to brittle transition range. A new high capacity irradiation rig was designed to meet the specific CT50 specimens loading requirements in the 70 MWth OSIRIS material testing reactor operated by CEA's Nuclear Energy Division at the Saclay Research Center. This paper presents the measurement and calculation developments required in these particular conditions. Spectrum characteristics and neutron flux levels were determined by a comprehensive dosimetry on mock-ups featuring activation foils and damage monitors. At the same time, a new calculation methodology based on the TRIPOLI-4.3 Monte Carlo code and IRDF-2002 dosimetry files was validated against calorimetric and neutron activation measurements.
Advances in Calculation of Fluence to Reactor Structures
Authors: Lippincott EP , Manahan MP
Published: December 2005

Accurate calculation of fluence to reactor structures involves integration of exposure over time taking into account changes in operating conditions and also estimation of the uncertainty in the calculation process. This paper reports on recent improvements we have made in calculation techniques and also on validation of those techniques by benchmarking against measurements in operating boiling water reactors (BWRs). Results and discussion of calculations in regions that fall outside the reactor beltline and thus require 3-D calculations to produce accurate results are presented.
Comparison of Predicted and Measured Helium Production in U.S. BWR Reactors
Authors: Greenwood LR , Oliver BM
Published: December 2005

Helium production in reactor steel is calculated as the summation of all neutron reactions that produce helium either with thermal or fast neutrons. Thermal helium production is due to elements or impurities that are known to have a thermal neutron cross section for helium production, including 10B and 59Ni. Fast neutrons produce helium in all materials due to the threshold (n, α) reactions as well as other reactions that include helium as one of the reaction products. A generalized equation is given for helium production in all reactor materials and comparisons are given for helium measurements in steel and inconel samples. The helium production calculated using the generalized equation is in good agreement with helium measurements in samples from BWR reactors. Simplified equations are given with numerical values and generic parameters to facilitate calculations. However, it is important to use the actual boron content when known to obtain reliable estimates of the helium production.
Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients
Authors: Rasmussen Lars Melholt , Tarnow Lise , Hansen Troels Krarup , Parving Hans-Henrik , Flyvbjerg Allan
Published: December 2005

Objective: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes.

Methods: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA.

Results: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49–3.99) vs 2.57 (2.19–3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine.

Conclusion: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.
Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism
Authors: Kobayashi Keisuke , Imanishi Yasuo , Miyauchi Akimitsu , Onoda Naoyoshi , Kawata Takehisa , Tahara Hideki , Goto Hitoshi , Miki Takami , Ishimura Eiji , Sugimoto Toshitsugu , Ishikawa Tetsuro , Inaba Masaaki , Nishizawa Yoshiki
Published: December 2005

Objective: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT).

Patients and methods: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)–PCR and immunohistochemistry.

Results: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23.

Conclusions: Serum calcium may regulate circulating FGF-23 levels in PHPT.
Ghrelin, insulin sensitivity and postprandial glucose disposal in overweight and obese children
Authors: Maffeis Claudio , Bonadonna Riccardo C , Consolaro Alessandro , Vettor Roberto , Banzato Claudia , Silvagni Davide , Bogoni Giovanna , Pellegrino Maristella , Tatò Luciano
Published: December 2005

Objective: To explore the changes of ghrelin circulating levels induced by a mixed meal and their relationship with postprandial substrate oxidation rates in overweight and obese children with different levels of insulin sensitivity.

Methods: A group of ten boys (age 9–12 years) with different levels of overweight (standard deviation score of body mass index: 1.6–3.2) was recruited. Body composition was measured by dual-energy X-ray absorptiometry. Insulin sensitivity was assessed by a frequently sampled i.v. glucose tolerance test. Pre-prandial and postprandial (3 h) substrate oxidation was measured by indirect calorimetry. The energy content of the test meal (16% protein, 36% carbohydrate and 48% fat) was 40% of pre-prandial energy expenditure (kJ/day).

Results: Pre-prandial serum concentration of total ghrelin was 701.4±66.9 pg/ml (S.E.M.). The test meal induced a rapid decrease in ghrelin levels and maximal decrease was 27.3±2.7% below baseline. Meal intake induced a progressive increase of the carbohydrate oxidation rate for 45 min after food ingestion, followed by a slow decrease without returning to pre-prandial values. Postprandial cumulative carbohydrate oxidation was 16.9±0.8 g/3 h. Insulin sensitivity and postprandial maximal decrease of ghrelin concentration showed a significant correlation (r = 0.803, P < 0.01). Moreover, the postprandial carbohydrate oxidation rate correlated with the area under the curve for both insulin (r = 0.673, P < 0.03) and ghrelin (r = −0.661, P < 0.04).

Conclusions: A relevant association between postprandial insulin-mediated glucose metabolism and ghrelin secretion in children with different levels of overweight was found. It is possible that the maintenance of an adequate level of insulin sensitivity and glucose oxidation may affect appetite regulation by favoring a more efficient postprandial ghrelin reduction.
Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines
Authors: Corbetta S , Angioni R , Cattaneo A , Beck-Peccoz P , Spada A
Published: December 2005

Objective:In vitroandin vivomodels indicate that all-transretinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-transretinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels.

Design: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 μg of acitretin.

Methods: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls.

Results: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 ± 0.034 versus 0.329 ± 0.051;P< 0.05) and HOMA-IR index (1.53 ± 0.73 versus 2.59 ± 1.41;P< 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 ± 11.7 versus 39.4 ± 10.4 mg/dl;P= 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 ± 4.4 versus 6.2 ± 2.1 ng/ml;P= 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor α (TNFα) levels, which persisted elevated throughout the treatment.

Conclusions: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFα levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.
Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys
Authors: Boas Malene , Boisen Kirsten A , Virtanen Helena E , Kaleva Marko , Suomi Anne-Maarit , Schmidt Ida M , Damgaard Ida N , Kai Claudia M , Chellakooty Marla , Skakkebæk Niels E , Toppari Jorma , Main Katharina M
Published: December 2005

Objective: Infant boys show a brief activation of their hypothalamic–pituitary–gonadal axis shortly after birth, the physiological significance of which is poorly understood. The objective of the study was to investigate the correlation between endogenous testosterone levels and penile size and growth.

Design: Prospective, longitudinal population-based study taking place at two large primary obstetric centres at the University Hospitals of Copenhagen, Denmark, and Turku, Finland.

Methods: Infant boys, 728 Danish and 1234 Finnish, underwent clinical examinations at 0, 3, 18 and 36 months in Denmark and at 0, 3 and 18 months in Finland with blood samples taken at 3 months (n = 630). Penile length and growth were registered and reproductive hormones (testosterone, sex hormone binding globulin, oestradiol) were analysed.

Results: Penile length increased from birth (3.49±0.4 cm) to 3 years of age (4.53±0.51 cm) with the highest growth velocity from birth to 3 months (1.0 mm/month). Penile length and growth were significantly, positively correlated to serum testosterone (r = 0.31 and 0.076, P = 0.006 and 0.001 respectively) and to free testosterone index (r = 0.385 and 0.094, P = 0.0001 and 0.0001 respectively).

Conclusions: We found that endogenous testosterone was significantly associated with penile size and growth rate in infant boys. Thus, the postnatal surge in reproductive hormones appears to be important for genital growth. Our data may serve as an updated reference for normal penile length in Caucasian boys up to 3 years of age.
Slush-Ice Storage of Catfish Carcasses
Authors: Bosworth Brian G , Wolters William R , Silva Juan L , Chamul Roberto S
Published: December 2005

This study evaluated the effects of 24-h slush-ice storage of carcasses of channel catfish Ictalurus punctatus on subsequent fillet yield, shape, and color. Channel catfish were sorted into three size-classes based on carcass (unskinned, with head and viscera removed) weight: small (250–425 g), medium (426–550 g), and large (551–1,000 g). In each of three replicate trials, 40 carcasses from each size-class were processed immediately after being killed (immediately processed treatment) and 40 carcasses from each size-class were held in ice water slush for 24 h and then processed (slush-ice treatment). Slush-ice-treated fish had higher unskinned fillet yield (+1.7%), skinned fillet yield (+1.2%), shank fillet yield (+0.6%), and nugget yield (+0.7%) than immediately processed fish. Measures of fillet yield increased in both treatments as carcass size increased. Immediately processed fillets were shorter (maximum distance anterior to posterior margin) and deeper (maximum distance from dorsal to ventral margin), and had less surface area than slush-ice fillets 24 h after slaughter. Sensory panelists perceived fillets from the slush-ice treatment to be larger than immediately processed fillets in 74% of comparisons of fillet pairs of equal weight. No fillet color differences were detected between treatments. Commercial catfish processors could increase fillet yield by storing carcasses in slush ice before filleting. However, costs associated with chilling and holding carcasses and quality issues, such as fillet drip-loss, texture, and shelf life, need to be addressed to determine whether slush-ice storage of carcasses will be beneficial to commercial catfish processors.
Fishing and Natural Mortality of Bluegills and Redear Sunfish at Lake Panasoffkee, Florida: Implications for Size Limits
Authors: Crawford S. , Allen M. S.
Published: December 2005

Growth, annual exploitation (u), and natural mortality (v) of bluegills Lepomis macrochirus and redear sunfish L. microlophus were investigated on Lake Panasoffkee, Florida, during 1998 and 1999 to assess the potential benefits of several minimum size limits. The average u of 15.0-cm total length (TL) or larger fish was 0.14 for bluegills and redear sunfish during the 2-year period. For both species, exploitation increased up to threefold as fish size increased (e.g., u = 0.37 for bluegills ≥23.0 cm TL in 1999). Total annual mortality (A) was 0.64 for bluegills and 0.68 for redear sunfish. Natural mortality estimates were 0.50 (78% of A) for bluegills and 0.55 (81% of A) for redear sunfish. Simulations predicted that minimum size limits would decrease average total yield and harvest for both bluegills and redear sunfish, but that a 20.3-cm minimum length limit could slightly increase the number of fish harvested over 20.0 cm TL. A 22.9-cm minimum length limit was predicted to greatly reduce yield without creating a measurable increase in the harvest of fish over the size limit. Lake Panasoffkee sunfishes incurred record levels of estimated effort and harvest in 1998–1999, but size-selective exploitation acted essentially as a minimum size limit, resulting in no predicted benefit for a 20.3-cm limit. Separation of fishing mortality and natural mortality allowed us to conclude that natural mortality had a greater influence on Lake Panasoffkee sunfish population abundance and fishing quality than did fishing mortality, so a minimum size limit was not recommended. Estimates of exploitation, natural mortality, and growth rates are more valuable than measures of size structure and angler catch when considering or evaluating harvest restrictions.
Anatomical Compartments Modify the Response of Human Hematopoietic Cells to a Mitogenic Signal
Authors: Nagasawa Yasuo , Wood Brent L. , Wang Linlin , Lintmaer Ingrid , Guo Wenjin , Papayannopoulou Thalia , Harkey Michael A. , Nourigat Cynthia , Blau C. Anthony
Published: December 2005

Methods for specifically regulating transplanted cells have many applications in gene and cell therapy. We examined the response of human cord blood CD34+ cells to a specific mitotic signal in vivo. Using a conditional signaling molecule (F36VMpl) that is specifically activated by an artificial ligand called a chemical inducer of dimerization (CID), human hematopoietic cells transplanted into immune deficient mice were induced to proliferate. Only differentiating erythroid precursors and multipotential and erythroid progenitors (colony-forming unit [CFU]-mix and burst forming unitserythroid [BFUe]) responded; however, the nature of the response differed markedly between bone marrow and spleen. In the marrow, F36VMpl induced a 12- to 17-fold expansion of differentiated erythroid precursors and a loss of CFU-mix and BFUe. In the spleen, F36VMpl induced a marked rise in BFUe and CFU-mix and, relative to marrow, a much less prominent rise in more mature red cells. Clonal analysis was most consistent with the interpretation that the spleen and bone marrow differentially regulate the response of human progenitors to a mitotic signal, possibly influencing progenitor expansion versus differentiation. These findings establish CIDs as in vivo growth factors for human hematopoietic cells.
Rethinking the Hispanic Paradox: Death Rates and Life Expectancy for US Non-Hispanic White and Hispanic Populations
Authors: Smith David P. , Bradshaw Benjamin S.
Published: December 2005

Objectives. We examined the “Hispanic paradox,” whereby persons of Hispanic origin seemed to experience lower mortality than the non-Hispanic White population. This paradox coincided with a change from the classification of deaths and population by Spanish surname to the use of Hispanic-origin questions in the census and vital statistics.

Methods. To estimate US Hispanic and non-Hispanic White mortality, we applied a familiar relation between death rates for population subgroups to Hispanic and non-Hispanic White population death rates. We calculated age-specific death rates for the Hispanic population and the non-Hispanic White population and computed life tables for each.

Result. For Texas between 1980 (surname) and 1990 (origin), the change in Hispanic deaths in persons aged 65 years or older was only half as great as the change in population size, implying a relative omission of 15% to 20% of deaths. By a different approach, the life tables for the US Hispanic and non-Hispanic White populations pointed to a similar omission.

Conclusions. There is no “Hispanic paradox.” The Hispanic paradox described in past research derives from inconsistencies in counts of Hispanic-origin deaths and populations.