bluuebunny/crossref_metadata_2025 huggingface dataset:
Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study
Authors: Toft Gunnar , Axmon Anna , Giwercman Aleksander , Thulstrup Ane Marie , Rignell-Hydbom Anna , Pedersen Henning Sloth , Ludwicki Jan K , Zvyezday Valentina , Zinchuk Andery , Spano Marcello , Manicardi Gian Carlo , Bonefeld-Jørgensen Eva C , Hagmar Lars , Bonde Jens Peter ,   INUENDO
Published: November 2005

Background

Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited.

Methods

Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample.

Results

Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5–0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0–1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw.

Conclusion

We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy.
A national, geographic database of CDC-funded HIV prevention services: development challenges and potential applications
Authors: Hanchette Carol L , Gibbs Deborah A , Gilliam Aisha , Fogarty Kieran J , Bruhn Mark
Published: November 2005

Background

From 2000–2002, the Centers for Disease Control and Prevention (CDC) funded a study that was designed to improve the information available to program planners about the geographic distribution of CDC-funded HIV prevention services provided by community-based organizations (CBOs). Program managers at CDC recognized the potential of a geographic information system (GIS) to organize and analyze information about HIV prevention services and they made GIS a critical component of the study design. The primary objective of this study was to construct a national, geographically-referenced database of HIV prevention services provided by CDC-funded CBOs. We designed a survey instrument to collect information about the geographic service areas where CBOs provided HIV prevention services, then collected data from CBOs that received CDC funding for these services during fiscal year 2000. We developed a GIS database to link questionnaire responses with GIS map layers in a manner that would incorporate overlapping geographies, risk populations and prevention services. We collected geographic service area data in two formats: 1) geopolitical boundaries and 2) geographic distance.

Results

The survey response rate was 70.3%, i.e. 1,020 of 1,450 community-based organizations responded. The number of HIV prevention programs administered by each CBO ranged from 1 to 23. The survey provided information about 3,028 prevention programs, including descriptions of intervention types, risk populations, race and ethnicity, CBO location and geographic service area. We incorporated this information into a large GIS database, the HIV Prevention Services Database. The use of geopolitical boundaries provided more accurate results than geographic distance. The use of a reference map with the questionnaire improved completeness, accuracy and precision of service area data.

Conclusion

The survey instrument design and database development procedures that we used for this study successfully met our objective. The development of the HIV Prevention Services Database for CDC is an important step toward the implementation of a spatial decision support system. Due to the costs involved in a nationwide survey such as this, we recommend that future data collection efforts use Web-based survey methodologies that incorporate interactive maps.
Coronary artery to left ventricle fistula
Authors: López-Candales Angel , Kumar Vivek
Published: November 2005

Background

Coronary cameral fistulas are an uncommon entity, the etiology of which may be congenital or traumatic. They involve abnormal termination of a coronary artery, usually the right coronary, into a cardiac chamber, usually the right ventricle.

Case Presentation

We describe a case of female patient with severe aortic stenosis and interventricular septal hypertrophy that underwent bioprosthetic aortic valve replacement with concomitant septal myectomy. On subsequent follow-up an abnormal flow traversing the septum into the left ventricle was identified and Doppler interrogation demonstrated a continuous flow, with a predominantly diastolic component, consistent with coronary arterial flow.

Conclusion

The literature on coronary cameral fistulas is reviewed and the etiology of the diagnostic findings discussed. In our patient, a coronary artery to left ventricle fistula was the most likely explanation secondary to trauma to the septal perforator artery during myectomy. Since the patient was asymptomatic at the time of diagnosis no intervention was recommended and has done well on follow-up.
Postoperative mortality after cancer surgery in octogenarians and nonagenarians: results from a series of 5,390 patients
Authors: Damhuis Ronald AM , Meurs Claudia JC , Meijer Willem S
Published: November 2005

Background

To support decisions about surgical treatment of elderly patients with cancer, population-based estimates of postoperative mortality (POM) rates are required.

Methods

Electronic records from the Rotterdam Cancer Registry were retrieved for octogenarians and nonagenarians who underwent resection in the period 1987–2000. POM was defined as death within 30 days of resection and both elective and emergency operations were included.

Results

In a series of 5.390 operated patients aged 80 years and older, POM rates were 0.5% for breast cancer, 1.7% for endometrial cancer and 4.2% for renal cancer. For patients with colorectal cancer, POM increased from 8% for the age group 80–84 to 13% for those 85–89 to 20% in nonagenarians. For stomach cancer, the respective figures were 11%, 20% and 44%.

Conclusion

These results show that resections can be performed at acceptable risk in selected elderly patients with cancer.
Mixed protocols: Multiple ratios of FSH and LH bioactivity using highly purified, human-derived FSH (BRAVELLE) and highly purified hMG (MENOPUR) are unaltered by mixing together in the same syringe
Authors: Scobey M Joseph , Raike Elizabeth , Marshall Dennis C
Published: November 2005

Background

The use of mixed or blended protocols, that utilize both FSH and hMG, for controlled ovarian hyperstimulation is increasing in use. To reduce the number of injections a patient must administer, many physicians instruct their patients to mix their FSH and hMG together to be given as a single injection. Therefore, the goal of this study was to definitively determine if the FSH and LH bioactivities of highly purified, human-derived FSH (Bravelle(R)) and highly purified hMG (Menopur(R)) were altered by reconstituting in 0.9% saline and mixing in the same syringe.

Methods

Bravelle(R) and Menopur(R) were reconstituted in 0.9% saline and mixed in a Becton Dickinson plastic syringe. The FSH and LH bioactivities of the products were determined after injecting female and male rats, respectively, with Bravelle(R), Menopur(R), or a mixture of Bravelle(R) and Menopur(R). Ratios of FSH:LH activity tested were 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)).

Results

There were no statistically significant changes in either FSH or LH bioactivity that occurred after mixing Bravelle(R) with Menopur(R) in the same syringe. The theoretical vs. actual FSH bioactivity for Bravelle(R) and Menopur(R) were 75 vs. 76.58 IU/mL and 75 vs. 76.0 IU/mL, respectively. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)) tested, the theoretical vs. actual FSH bioactivities were 150 vs. 156.86 IU/mL, 300 vs. 308.69 IU/mL and 300 vs. 306.58 IU/mL, respectively. The theoretical vs. actual LH bioactivity for Menopur(R) in the above mentioned ratios tested were 75 vs. 77.50 IU/mL. For the 3 ratios of FSH:LH activity tested, 150:75 IU (1 vial Bravelle(R): 1 vial Menopur(R)), 300:75 IU (3 vials Bravelle(R): 1 vial Menopur(R)) or 300:225 IU (1 vial Bravelle(R): 3 vials of Menopur(R)), the theoretical vs. actual LH bioactivities were 75 vs. 78.38 IU/mL, 75 vs. 78.63 IU/mL and 225 vs. 233.48 IU/mL, respectively.

Conclusion

Mixing human-derived FSH (Bravelle(R)) with highly purified hMG (Menopur(R)) in the same diluent, 0.9% NaCL, does not alter the FSH or LH bioactivity of either gonadotropin preparation.
Tat gets the "green" light on transcription initiation
Authors: Brady John , Kashanchi Fatah
Published: November 2005

Human immunodeficiency virus type 1 (HIV-1) Tat transactivation is an essential step in the viral life cycle. Over the past several years, it has become widely accepted that Tat exerts its transcriptional effect by binding the transactivation-responsive region (TAR) and enhancing transcriptional elongation. Consistent with this hypothesis, it has been shown that Tat promotes the binding of P-TEFb, a transcription elongation factor composed of cyclin T1 and cdk9, and the interaction of Tat with P-TEFb and TAR leads to hyperphosphorylation of the C-terminal domain (CTD) of RNA Pol II and increased processivity of RNA Pol II. A recent report, however, has generated renewed interest that Tat may also play a critical role in transcription complex (TC) assembly at the preinitiation step. Using in vivo chromatin immunoprecipitation assays, the authors reported that the HIV TC contains TBP but not TBP-associated factors. The stimulatory effect involved the direct interaction of Tat and P-TEFb and was evident at the earliest step of TC assembly, the TBP-TATA box interaction. In this article, we will review this data in context of earlier data which also support Tat's involvement in transcriptional complex assembly. Specifically, we will discuss experiments which demonstrated that Tat interacted with TBP and increased transcription initiation complex stability in cell free assays. We will also discuss studies which demonstrated that over expression of TBP alone was sufficient to obtain Tat activated transcription in vitro and in vivo. Finally, studies using self-cleaving ribozymes which suggested that Tat transactivation was not compatible with pausing of the RNA Pol II at the TAR site will be discussed.
Differential direct effects of cyclo-oxygenase-1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitrostudy
Authors: Mastbergen Simon C , Jansen Nathalie WD , Bijlsma Johannes WJ , Lafeber Floris PJG
Published: November 2005

Treatment of osteoarthritis (OA) with nonsteroidal anti-inflammatory drugs (NSAIDs) diminishes inflammation along with mediators of cartilage destruction. However, NSAIDs may exert adverse direct effects on cartilage, particularly if treatment is prolonged. We therefore compared the direct effects of indomethacin, naproxen, aceclofenac and celecoxib on matrix turnover in human OA cartilage tissue. Human clinically defined OA cartilage from five different donors was exposed for 7 days in culture to indomethacin, naproxen, aceclofenac and celecoxib – agents chosen based on their cyclo-oxygenase (COX)-2 selectivity. As a control, SC-560 (a selective COX-1 inhibitor) was used. Changes in cartilage proteoglycan turnover and prostaglandin E2production were determined. OA cartilage exhibited characteristic proteoglycan turnover. Indomethacin further inhibited proteoglycan synthesis; no significant effect of indomethacin on proteoglycan release was found, and proteoglycan content tended to decrease. Naproxen treatment was not associated with changes in any parameter. In contrast, aceclofenac and, prominently, celecoxib had beneficial effects on OA cartilage. Both were associated with increased proteoglycan synthesis and normalized release. Importantly, both NSAIDs improved proteoglycan content. Inhibition of prostaglandin E2production indirectly showed that all NSAIDs inhibited COX, with the more COX-2 specific agents having more pronounced effects. Selective COX-1 inhibition resulted in adverse effects on all parameters, and prostaglandin E2production was only mildly inhibited. NSAIDs with low COX-2/COX-1 selectivity exhibit adverse direct effects on OA cartilage, whereas high COX-2/COX-1 selective NSAIDs did not show such effects and might even have cartilage reparative properties.
Effects of combined treatment with rapamycin and cotylenin A, a novel differentiation-inducing agent, on human breast carcinoma MCF-7 cells and xenografts
Authors: Kasukabe Takashi , Okabe-Kado Junko , Kato Nobuo , Sassa Takeshi , Honma Yoshio
Published: November 2005

Introduction

Rapamycin, an inhibitor of the serine/threonine kinase target of rapamycin, induces G1 arrest and/or apoptosis. Although rapamycin and its analogues are attractive candidates for cancer therapy, their sensitivities with respect to growth inhibition differ markedly among various cancer cells. Using human breast carcinoma cell line MCF-7 as an experimental model system, we examined the growth-inhibitory effects of combinations of various agents and rapamycin to find the agent that most potently enhances the growth-inhibitory effect of rapamycin.

Method

We evaluated the growth-inhibitory effect of rapamycin plus various agents, including cotylenin A (a novel inducer of differentiation of myeloid leukaemia cells) to MCF-7 cells, using either MTT assay or trypan blue dye exclusion test. The cell cycle was analyzed using propidium iodide-stained nuclei. Expressions of several genes in MCF-7 cells with rapamycin plus cotylenin A were studied using cDNA microarray analysis and RT-PCR. The in vitro results of MCF-7 cells treated with rapamycin plus cotylenin A were further confirmed in vivo in a mouse xenograft model.

Results

We found that the sensitivity of rapamycin to MCF-7 cells was markedly affected by cotylenin A. This treatment induced growth arrest of the cells at the G1 phase, rather than apoptosis, and induced senescence-associated β-galactosidase activity. We examined the gene expression profiles associated with exposure to rapamycin and cotylenin A using cDNA microarrays. We found that expressions of cyclin G2, transforming growth factor-β-induced 68 kDa protein, BCL2-interacting killer, and growth factor receptor-bound 7 were markedly induced in MCF-7 cells treated with rapamycin plus cotylenin A. Furthermore, combined treatment with rapamycin and cotylenin A significantly inhibited the growth of MCF-7 cells as xenografts, without apparent adverse effects.

Conclusion

Rapamycin and cotylenin A cooperatively induced growth arrest in breast carcinoma MCF-7 cells in vitro, and treatment with rapamycin and cotylenin A combined more strongly inhibited the growth of MCF-7 cells as xenografts in vivo than treatment with rapamycin or cotylenin A alone, suggesting that this combination may have therapeutic value in treating breast cancer. We also identified several genes that were markedly modulated in MCF-7 cells treated with rapamycin plus cotylenin A.
Antisense oligonucleotides targeting the progesterone receptor inhibit hormone-independent breast cancer growth in mice
Authors: Lamb Caroline A , Helguero Luisa A , Giulianelli Sebastián , Soldati Rocío , Vanzulli Silvia I , Molinolo Alfredo , Lanari Claudia
Published: November 2005

Introduction

Previous data from our laboratory suggested that progesterone receptors (PRs) are involved in progestin-independent growth of mammary carcinomas. To investigate this possibility further, we studied the effects of PR antisense oligodeoxynucleotides (asPR) on in vivo tumor growth.

Method

BALB/c mice with subcutaneous 25 mm2 mammary carcinomas expressing estrogen receptor-α and PR were either injected intraperitoneally with 1 mg asPR every 24 or 12 hours for 5–10 days, or subcutaneously with RU 486 (6.5 mg/kg body weight) every 24 hours. Control mice received vehicle or scPR.

Results

Significant inhibition of tumor growth as well as a significant decrease in bromodeoxyuridine uptake was observed in asPR-treated mice, which correlated with histological signs of regression and increased apoptosis. Mice treated with RU 486 experienced almost complete tumor regression. No differences were detected between vehicle-treated and scPR-treated mice. Anti-progestin-treated and asPR-treated mice were in a continuous estrous/meta-estrous state. Decreased phosphorylated extracellular signal-regulated kinase (ERK)1 and ERK2 levels and estrogen receptor-α expression were observed as late events in RU 486-treated and asPR-treated mice with regressing tumors.

Conclusion

We demonstrate, for the first time, inhibition of tumor growth in vivo using asPR. Our results provide further evidence for a critical and hierarchical role of the PR pathway in mammary carcinomas.
Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells
Authors: Zhang Yanhong , Pan Quintin , Zhong Hui , Merajver Sofia D , Kleer Celina G
Published: November 2005

Introduction

CCN6/WISP3 belongs to the CCN (Cyr61, CTGF, Nov) family of genes that contains a conserved insulin-like growth factor (IGF) binding protein motif. CCN6 is a secreted protein lost in 80% of the aggressive inflammatory breast cancers, and can decrease mammary tumor growth in vitro and in vivo. We hypothesized that inhibition of CCN6 might result in the loss of a growth regulatory function that protects mammary epithelial cells from the tumorigenic effects of growth factors, particularly IGF-1.

Method

We treated human mammary epithelial (HME) cells with a CCN6 hairpin short interfering RNA.

Results

CCN6-deficient cells showed increased motility and invasiveness, and developed features of epithelial-mesenchymal transition (EMT). Inhibition of CCN6 expression promoted anchorage-independent growth of HME cells and rendered them more responsive to the growth effects of IGF-1, which was coupled with the increased phosphorylation of IGF-1 receptor and insulin receptor substrate-1 (IRS-1).

Conclusion

Specific stable inhibition of CCN6 expression in HME cells induces EMT, promotes anchorage-independent growth, motility and invasiveness, and sensitizes mammary epithelial cells to the growth effects of IGF-1.
Breast cancer histological classification: agreement between the Office for National Statistics and the National Health Service Breast Screening Programme
Authors: Gathani Toral , Bull Diana , Green Jane , Reeves Gillian , Beral Valerie ,   the Million Women Study Collaborators
Published: November 2005

Introduction

Epidemiological studies rely on data supplied by central cancer registration sources to be timely, accurate and complete. Validation studies of such data at a national level are limited. Data collected for the Million Women Study was used to compare the level of agreement between the Office for National Statistics (ONS) and the National Health Service Breast Screening Programme (NHSBSP) in the recording of incident screen-detected breast cancer histology between 1996 and 2001.

Methods

1.3 million women aged 50 to 64 years were recruited into the Million Women Study cohort via the NHSBSP. Incident screen-detected breast cancer histologies were notified separately by the ONS and NHSBSP. ICD-10 and ICD-02 ONS codes and NHSBSP histology data were similarly coded to allow for comparison in terms of cancer invasiveness and morphology. The statistical outcome measures are percentage agreement and the kappa statistic.

Results

A total of 5,886 incident screen-detected breast cancers were available for analysis. Of the 5,886 screen-detected cancers reported by the ONS and NHSBSP, 5,684 (96.6%, κ = 0.9) agreed in terms of the degree of invasiveness. Of the 5,458 cancers that had been assigned a specific morphology code, there was exact agreement between the ONS and the NHSBSP in 4,922 cases (90.2%, κ = 0.8).

Conclusion

There is an excellent level of agreement between the ONS and NHSBSP in the recording of the histology of screen-detected breast cancer. From these results it is not possible to comment on which source of data is the more or less accurate, although the differences are very small.
Early veno-venous haemodiafiltration for sepsis-related multiple organ failure
Authors: Page Bernard , Vieillard-Baron Antoine , Chergui Karim , Peyrouset Olivier , Rabiller Anne , Beauchet Alain , Aegerter Philippe , Jardin François
Published: November 2005

Introduction

We conducted a prospective observational study from January 1995 to December 2004 to evaluate the impact on recovery of a major advance in renal replacement therapy, namely continuous veno-venous haemodiafiltration (CVVHDF), in patients with refractory septic shock.

Method

CVVHDF was implemented after 6–12 hours of maximal haemodynamic support, and base excess monitoring was used to evaluate the improvement achieved. Of the 60 patients studied, 40 had improved metabolic acidosis after 12 hours of CVVHDF, with a progressive improvement in all failing organs; the final mortality rate in this subgroup was 30%. In contrast, metabolic acidosis did not improve in the remaining 20 patients after 12 hours of CVVHDF, and the mortality rate in this subgroup was 100%. The crude mortality rate for the whole group was 53%, which is significantly lower than the predicted mortality using Simplified Acute Physiology Score II (79%).

Conclusion

Early CVVHDF may improve the prognosis of sepsis-related multiple organ failure. Failure to correct metabolic acidosis rapidly during the procedure was a strong predictor of mortality.
Steroid-dependent modification of Hox function drives myocyte reprogramming in theDrosophilaheart
Authors: Monier Bruno , Astier Martine , Sémériva Michel , Perrin Laurent
Published: November 2005

In the Drosophila larval cardiac tube, aorta and heart differentiation are controlled by the Hox genes Ultrabithorax(Ubx) and abdominal A (abdA), respectively. There is evidence that the cardiac tube undergoes extensive morphological and functional changes during metamorphosis to form the adult organ, but both the origin of adult cardiac tube myocytes and the underlying genetic control have not been established. Using in vivo time-lapse analysis, we show that the adult fruit fly cardiac tube is formed during metamorphosis by the reprogramming of differentiated and already functional larval cardiomyocytes,without cell proliferation. We characterise the genetic control of the process, which is cell autonomously ensured by the modulation of Ubxexpression and AbdA activity. Larval aorta myocytes are remodelled to differentiate into the functional adult heart, in a process that requires the regulation of Ubx expression. Conversely, the shape, polarity,function and molecular characteristics of the surviving larval contractile heart myocytes are profoundly transformed as these cells are reprogrammed to form the adult terminal chamber. This process is mediated by the regulation of AbdA protein function, which is successively required within these persisting myocytes for the acquisition of both larval and adult differentiated states. Importantly, AbdA specificity is switched at metamorphosis to induce a novel genetic program that leads to differentiation of the terminal chamber. Finally, the steroid hormone ecdysone controls cardiac tube remodelling by impinging on both the regulation of Ubx expression and the modification of AbdA function. Our results shed light on the genetic control of one in vivo occurring remodelling process, which involves a steroid-dependent modification of Hox expression and function.
Directed differentiation of neural cells to hypothalamic dopaminergic neurons
Authors: Ohyama Kyoji , Ellis Pamela , Kimura Shioko , Placzek Marysia
Published: November 2005

Hypothalamic neurons play a key role in homeostasis, yet little is known about their differentiation. Here, we demonstrate that Shh and Bmp7 from the adjacent prechordal mesoderm govern hypothalamic neural fate, their sequential action controlling hypothalamic dopaminergic neuron generation in a Six3-dependent manner. Our data suggest a temporal distinction in the requirement for the two signals. Shh acts early to specify dopaminergic neurotransmitter phenotype. Subsequently, Bmp7 acts on cells that are ventralised by Shh, establishing aspects of hypothalamic regional identity in late-differentiating/postmitotic cells. The concerted actions of Shh and Bmp7 can direct mouse embryonic stem cell-derived neural progenitor cells to a hypothalamic dopaminergic fate ex vivo.
Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation
Authors: Koziel Lydia , Wuelling Manuela , Schneider Sabine , Vortkamp Andrea
Published: November 2005

During endochondral ossification, the secreted growth factor Indian hedgehog (Ihh) regulates several differentiation steps. It interacts with a second secreted factor, parathyroid hormone-related protein (PTHrP), to regulate the onset of hypertrophic differentiation, and it regulates chondrocyte proliferation and ossification of the perichondrium independently of PTHrP. To investigate how the Ihh signal is translated in the different target tissues, we analyzed the role of the zinc-finger transcription factor Gli3, which acts downstream of hedgehog signals in other organs. Loss of Gli3 in Ihh mutants restores chondrocyte proliferation and delays the accelerated onset of hypertrophic differentiation observed in Ihh–/– mutants. Furthermore the expression of the Ihh target genes patched (Ptch) and PTHrP is reactivated in Ihh–/–;Gli3–/–mutants. Gli3 seems thus to act as a strong repressor of Ihh signals in regulating chondrocyte differentiation. In addition, loss of Gli3 in mice that overexpress Ihh in chondrocytes accelerates the onset of hypertrophic differentiation by reducing the domain and possibly the level of PTHrP expression.

Careful analysis of chondrocyte differentiation in Gli3–/– mutants revealed that Gli3 negatively regulates the differentiation of distal, low proliferating chondrocytes into columnar, high proliferating cells. Our results suggest a model in which the Ihh/Gli3 system regulates two distinct steps of chondrocyte differentiation:(1) the switch from distal into columnar chondrocytes is repressed by Gli3 in a PTHrP-independent mechanism; (2) the transition from proliferating into hypertrophic chondrocytes is regulated by Gli3-dependent expression of PTHrP. Furthermore, by regulating distal chondrocyte differentiation,Gli3 seems to position the domain of PTHrP expression.
Mis-specified cells die by an active gene-directed process, and inhibition of this death results in cell fate transformation inDrosophila
Authors: Werz Christian , Lee Tom V. , Lee Peter L. , Lackey Melinda , Bolduc Clare , Stein David S. , Bergmann Andreas
Published: November 2005

Incorrectly specified or mis-specified cells often undergo cell death or are transformed to adopt a different cell fate during development. The underlying cause for this distinction is largely unknown. In many developmental mutants in Drosophila, large numbers of mis-specified cells die synchronously, providing a convenient model for analysis of this phenomenon. The maternal mutant bicoid is particularly useful model with which to address this issue because its mutant phenotype is a combination of both transformation of tissue (acron to telson) and cell death in the presumptive head and thorax regions. We show that a subset of these mis-specified cells die through an active gene-directed process involving transcriptional upregulation of the cell death inducer hid. Upregulation of hid also occurs in oskar mutants and other segmentation mutants. In hid bicoid double mutants, mis-specified cells in the presumptive head and thorax survive and continue to develop, but they are transformed to adopt a different cell fate. We provide evidence that the terminal torso signaling pathway protects the mis-specified telson tissue in bicoid mutants from hid-induced cell death,whereas mis-specified cells in the head and thorax die, presumably because equivalent survival signals are lacking. These data support a model whereby mis-specification can be tolerated if a survival pathway is provided,resulting in cellular transformation.
Pelota controls self-renewal of germline stem cells by repressing a Bam-independent differentiation pathway
Authors: Xi Rongwen , Doan Choung , Liu Dazhi , Xie Ting
Published: November 2005

In the Drosophila ovary, germline stem cell (GSC) self-renewal is controlled by both extrinsic and intrinsic factors. The Bmp signal from niche cells controls GSC self-renewal by directly repressing a Bam-dependent differentiation pathway in GSCs. pelota (pelo), which has been previously shown to be required for Drosophila male meiosis, was identified in our genetic screen as a dominant suppressor of the dppoverexpression-induced GSC tumor phenotype. In this study, we reveal the unexpected new role of Pelo in controlling GSC self-renewal by repressing a Bam-independent differentiation pathway. In pelo mutant ovaries, GSCs are lost rapidly owing to differentiation. Results from genetic mosaic analysis and germ cell-specific rescue show that it functions as an intrinsic factor to control GSC self-renewal. In pelo mutant GSCs, Bmp signaling activity detected by Dad-lacZ expression is downregulated,but bam expression is still repressed. Furthermore, bammutant germ cells are still able to differentiate into cystocytes without pelo function, indicating that Pelo is involved in repressing a Bam-independent differentiation pathway. Consistent with its homology to the eukaryotic translation release factor 1α, we show that Pelo is localized to the cytoplasm of the GSC. Therefore, Pelo controls GSC self-renewal by repressing a Bam-independent differentiation pathway possibly through regulating translation. As Pelo is highly conserved from Drosophilato mammals, it may also be involved in the regulation of adult stem cell self-renewal in mammals, including humans.
Dysfunctional cilia lead to altered ependyma and choroid plexus function,and result in the formation of hydrocephalus
Authors: Banizs Boglarka , Pike Martin M. , Millican C. Leigh , Ferguson William B. , Komlosi Peter , Sheetz James , Bell Phillip D. , Schwiebert Erik M. , Yoder Bradley K.
Published: November 2005

Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelum, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.
Breakdown of abdominal patterning in the Tribolium Krüppel mutant jaws
Authors: Cerny Alexander C. , Bucher Gregor , Schröder Reinhard , Klingler Martin
Published: November 2005

During Drosophila segmentation, gap genes function as short-range gradients that determine the boundaries of pair-rule stripes. A classical example is Drosophila Krüppel (Dm'Kr) which is expressed in the middle of the syncytial blastoderm embryo. Patterning defects in Dm'Kr mutants are centred symmetrically around its bell-shaped expression profile. We have analysed the role of Krüppel in the short-germ beetle Tribolium castaneum where the pair-rule stripes corresponding to the 10 abdominal segments arise during growth stages subsequent to the blastoderm. We show that the previously described mutation jaws is an amorphic Tc'Kr allele. Pair-rule gene expression in the blastoderm is affected neither in the amorphic mutant nor in Tc'Kr RNAi embryos. Only during subsequent growth of the germ band does pair-rule patterning become disrupted. However, only segments arising posterior to the Tc'Kr expression domain are affected, i.e. the deletion profile is asymmetric relative to the expression domain. Moreover,stripe formation does not recover in posterior abdominal segments, i.e. the Tc'Krjaws phenotype does not constitute a gap in segment formation but results from a breakdown of segmentation past the 5th eve stripe. Alteration of pair-rule gene expression in Tc'Krjaws mutants does not suggest a direct role of Tc'Kr in defining specific stripe boundaries as in Drosophila. Together, these findings show that the segmentation function of Krüppel in this short-germ insect is fundamentally different from its role in the long-germ embryo of Drosophila. The role of Tc'Kr in Hox gene regulation, however, is in better accordance to the Drosophila paradigm.
Application of the multidisciplinary design optimization algorithm to the design of a belt-integrated seat while considering crashworthiness
Authors: Shin M K , Kang B S , Park G J
Published: November 2005

Multidisciplinary design optimization based on independent subspaces (MDOIS), which is a multidisciplinary design optimization (MDO) algorithm, has been recently proposed. Since MDOIS is relatively simple compared with other MDO algorithms, it is easy to apply MDOIS to practical engineering problems. In this research, an MDO problem is defined for the design of a belt-integrated seat (BIS) while considering crashworthiness. The crash model consists of an airbag, a BIS, an energy-absorbing steering system, and a safety belt. It is found that the current design problem has two disciplines - structural non-linear analysis and occupant analysis. The interdisciplinary relationship between the disciplines is identified. Interdisciplinary variables between the two disciplines are stiffness of the seat back frame and the belt load. The interdisciplinary relationship is addressed in the system analysis step in MDOIS. Prior to each independent subspace design, values of interdisciplinary variables at a given design point are determined in the system analysis step. The determined values are passed to corresponding subspaces, and the subspaces treat the received values of the interdisciplinary variables as constant parameters throughout the subspace design. For the present example, the belt load is passed to the structural analysis subspace and the stiffness of the seat back frame is passed to the occupant analysis subspace. Determined design variables in each subspace are passed to the system analysis step. In this way, the design process iterates until the convergence criterion is satisfied. As a result of the design, the weight of the BIS and the head injury criterion (HIC) of an occupant are reduced while the specified constraints are satisfied. Since the system analysis cannot be formulated in an explicit form in the current example, an optimization problem is formulated to solve the system analysis. The results from MDOIS are discussed.
The relationship of seat backrest angle and neck injury in low-velocity rear impacts
Authors: Latchford J , Chirwa E C , Chen T , Mao M
Published: November 2005

Car-rear-impact-induced cervical spine injuries present a serious burden on society and, in response, seats offering enhanced protection have been introduced. Seats are evaluated for neck protection performance but only at one specific backrest angle, whereas in the real world this varies greatly owing to the variation in occupant physique. Changing the backrest angle modifies the seat geometry and thereby the nature of its interaction with the occupant.

Low-velocity rear-impact tests on a BioRID II anthropomorphic test dummy (ATD) have shown that changes in backrest angle have a significant proportionate effect on dummy kinematics. A close correlation was found between changes in backrest angle and the responses of neck injury predictors such as lower neck loading and lower neck shear but not for the neck injury criterion NICmax. Torso ramping was evident, however, with negligible effect in low-velocity impacts.

The backrest angle ranged from 20° to 30° whereas the BioRID II spine was adapted to a range from 20° to 26.5°. Nevertheless, in general, instrumentation outputs correlated well, indicating that this ATD could be used for evaluating seats over a 20–30° range rather than solely at 25° as required by current approval test specifications.
Numerical analysis of a small European vehicle under rollover condition
Authors: Mao M , Chirwa E C , Chen T , Latchford J , Wang W
Published: November 2005

Quasi-static and dynamic roof crush simulations have been carried out successfully on a small European car that was loaded at different pitch/roll angles. The results obtained were validated against the MIRA experimental dynamic roof crush outputs and against the Bolton experiments performed under FMVSS 216. Overall, the outcomes show that bonded windscreens contribute to nearly 30 per cent of the roof strength, thus confirming similar results obtained by a number of other researchers. Furthermore, these results show that roof strength is a function of roll and pitch angles which also greatly influence the overall intrusion rate. The new findings illustrate that, having a fixed loading pitch angle, the roof strength decreases when the roll angles are between 15 and 45°. If the pitch angle is increased, the same phenomenon of reduced strength is observed. However, this does not signify that the roof becomes weaker with increasing pitch angle, because there are limits within which this can occur, and hence the worst-case loading that yields the smallest strength is found at pitch 10° and roll 45. Therefore, it is recommended in this paper that an update be made to the FMVSS 216, where a roll angle of 45° (not 25°) and a pitch angle of 10° (not 5°) be used as they constitute the worst-case loading condition. As a result, a more realistic test configuration with angles that replicate real-world accident data can be represented.
Investigation of the dynamic characteristics of suspension parameters on a vehicle experiencing steering drift during braking
Authors: Mirza N , Hussain K , Day A J , Klaps J
Published: November 2005

This paper presents a simulation study into the characteristics of a vehicle experiencing steering drift under straight line braking. Simulation modelling has been performed using a multi-body dynamics analysis based on a model of an actual vehicle. Front and rear suspension parameters have been modelled as rigid links joined with flexible bushes so as to assess their effect on a vehicle while braking. Suspension geometry and alignment settings, which define characteristic responses such as lateral acceleration, yaw velocity, toe, and caster angles of a vehicle in a transient manoeuvre, are primary to a vehicle's directional stability. Any symmetric inconsistencies in these settings will potentially affect a vehicle's performance. The findings from this research have increased the understanding of the causes of steering drift during braking conditions.
Development of a new calibration and monitoring system for in-vehicle electronic control units based on controller area network calibration protocol
Authors: Wang J-X , Feng J , Mao X-J , Yang L , Zhou B
Published: November 2005

An interactive user-friendly calibration and monitoring system is critical for the development of electronic control units (ECU). In this study, a controller area network (CAN) driver, CAN calibration protocol (CCP) driver, monitoring program, and calibration program in the ECU were designed with the assembly language. The inquiry mode was used in monitoring the program and the interrupt mode was used in the calibration program, which ensured the real-time, simultaneous communication and interruption for the main control program. Mirror memory and the random access memory (RAM) calibration technique were used to reduce the write and read accesses to ECU, and, with the mapping of calibration RAM, calibration parameters could be changed online and used instantly. An efficient database management was used to achieve an accurate dynamic link between PC and ECU. The present system provides reliable, accurate, and quick CAN communication between ECU and PC, with a baud rate up to 500K bit/s. It also provides a friendly, compatible, and flexible calibration interface, and the functions of online calibration and real-time monitoring. This system has been used successfully in high-pressure, common rail, electronically controlled diesel engines and pure electrical vehicles (after a small modification).
Development of a disc-type torque meter for an automatic transmission vehicle
Authors: Lee J Y , Kauh S K , Ha K-P
Published: November 2005

Torque is one of the key factors in describing engine performance. It is distributed to various parts of the vehicle such as the valvetrain, generator, and water pump. However, the exact torque delivered to each part cannot be determined. The first step to a full understanding of torque distribution is direct measurement of engine output torque. This paper considers the development of a disc-type torque meter that can be installed in a real vehicle. It uses the elastic deformation of a torque sensor which replaces the driveplate. It consists of a strain node, a power node, and a telemetry node, and transmits the torque signal by Bluetooth technology. The developed disc-type torque meter has good linearity and thermostability. It was installed in an in-line four-cylinder engine vehicle, and successfully measured the engine output torque.
An analytical study on heat transfer performance of radiators with non-uniform airflow distribution
Authors: Ng E Y , Johnson P W , Watkins S
Published: November 2005

Heat exchangers used in modern automobiles usually have a highly non-uniform air velocity distribution because of the complexity of the engine compartment and underhood flow fields; hence ineffective use of the core area has been noted. To adequately predict the heat transfer performance in typical car radiators, a generalized analytical model accounting for airflow maldistribution was developed using a finite element approach and applying appropriate heat transfer equations including the ε-NTU (effectiveness - number of heat transfer units) method with the Davenport correlation for the air-side heat transfer coefficient. The analytical results were verified against a set of experimental data from nine radiators tested in a wind tunnel and were found to be within +24 and −10 per cent of the experimental results. By applying the analytical model, several severe non-uniform velocity distributions were also studied. It was found that the loss of radiator performance caused by airflow maldistribution, compared with uniform airflow of the same total flowrate, was relatively minor except under extreme circumstances where the non-uniformity factor was larger than 0.5.

The relatively simple set of equations presented in this paper can be used independently in spreadsheets or in conjunction with computational fluid dynamics (CFD) analysis, enabling a full numerical prediction of aerodynamic as well as thermodynamic performance of radiators to be conducted prior to a prototype being built.
Male sex workers in Antwerp, Belgium: a descriptive study
Authors: Leuridan E , Wouters K , Stalpaert M , Van Damme P
Published: November 2005

The objective of this study was to describe the prevalence of sexually transmitted infections (STI), sociodemographic and behavioural characteristics in a population of male sex workers (MSW) in Antwerp, Belgium. Between September 1999 and March 2004, 129 MSW were reached by Gh@pro, an outreach programme providing preventive health care, free STI check-up and hepatitis B vaccination, to sex workers (SW). Sera were collected from 121 men, urine samples from 115 men and a questionnaire was filled in by 43 MSW. In 45.5% of MSW one or more STI were diagnosed (including hepatitis B), 76% on laboratory testing at first screening, 9% through symptomatology at first visit. The prevalence of HIV was 10.8%, hepatitis B virus (HBV) infection 28.9%, syphilis 12.5%, gonorrhoea 1.7% and Chlamydia trachomatis 9.7%. More than 50% of non-immune MSW completed their three-dose hepatitis B vaccination course. Prevalence of STI is concordant with published data on MSW; this population clearly requests and deserves particular attention and approach. There is an important difference in sociodemographic and behavioural characteristics between MSW working in the red light district and those working on the street. Health promotion should be tailored to the different subpopulations and outreach appears to be a successful tool.
A case of penile superficial basal cell carcinoma involving the inner surface of foreskin
Authors: Manavi K , Kemmett D
Published: November 2005

Basal cell carcinoma accounts for most skin malignancies. Genital basal cell carcinoma, however, is very rare. We report the first case of superficial basal cell carcinoma involving the inner surface of foreskin. Shared expertise within a multidisciplinary clinic was necessary for early diagnosis of the present case.