bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Tumor Metastasis by a Growth Factor Receptor Bound Protein 2 Src Homology 2 Domain–Binding Antagonist
Authors: Giubellino Alessio , Gao Yang , Lee Sunmin , Lee Min-Jung , Vasselli James R. , Medepalli Sampath , Trepel Jane B. , Burke Terrence R. , Bottaro Donald P.
Published: July 2007

Metastasis, the primary cause of death in most forms of cancer, is a multistep process whereby cells from the primary tumor spread systemically and colonize distant new sites. Blocking critical steps in this process could potentially inhibit tumor metastasis and dramatically improve cancer survival rates; however, our understanding of metastasis at the molecular level is still rudimentary. Growth factor receptor binding protein 2 (Grb2) is a widely expressed adapter protein with roles in epithelial cell growth and morphogenesis, as well as angiogenesis, making it a logical target for anticancer drug development. We have previously shown that a potent antagonist of Grb2 Src homology-2 domain–binding, C90, blocks growth factor–driven cell motility in vitro and angiogenesis in vivo. We now report that C90 inhibits metastasis in vivo in two aggressive tumor models, without affecting primary tumor growth rate. These results support the potential efficacy of this compound in reducing the metastatic spread of primary solid tumors and establish a critical role for Grb2 Src homology-2 domain–mediated interactions in this process. [Cancer Res 2007;67(13):6012–6]
Superoxide Signaling Mediates N-acetyl-l-cysteine–Induced G1 Arrest: Regulatory Role of Cyclin D1 and Manganese Superoxide Dismutase
Authors: Menon Sarita G. , Sarsour Ehab H. , Kalen Amanda L. , Venkataraman Sujatha , Hitchler Michael J. , Domann Frederick E. , Oberley Larry W. , Goswami Prabhat C.
Published: July 2007

Thiol antioxidants, including N-acetyl-l-cysteine (NAC), are widely used as modulators of the intracellular redox state. We investigated the hypothesis that NAC-induced reactive oxygen species (ROS) signaling perturbs cellular proliferation by regulating the cell cycle regulatory protein cyclin D1 and the ROS scavenging enzyme Mn–superoxide dismutase (MnSOD). When cultured in media containing NAC, mouse fibroblasts showed G1 arrest with decreased cyclin D1 protein levels. The absence of a NAC-induced G1 arrest in fibroblasts overexpressing cyclin D1 (or a nondegradable mutant of cyclin D1-T286A) indicates that cyclin D1 regulates this G1 arrest. A delayed response to NAC exposure was an increase in both MnSOD protein and activity. NAC-induced G1 arrest is exacerbated in MnSOD heterozygous fibroblasts. Results from electron spin resonance spectroscopy and flow cytometry measurements of dihydroethidine fluorescence showed an approximately 2-fold to 3-fold increase in the steady-state levels of superoxide (O2•−) in NAC-treated cells compared with control. Scavenging of O2•− with Tiron reversed the NAC-induced G1 arrest. These results show that an O2•− signaling pathway regulates NAC-induced G1 arrest by decreasing cyclin D1 protein levels and increasing MnSOD activity. [Cancer Res 2007;67(13):6392–9]
Delivery of 5-Aza-2′-Deoxycytidine to Cells Using Oligodeoxynucleotides
Authors: Yoo Christine B. , Jeong Shinwu , Egger Gerda , Liang Gangning , Phiasivongsa Pasit , Tang Chunlin , Redkar Sanjeev , Jones Peter A.
Published: July 2007

The major goal of epigenetic therapy is to reverse aberrant promoter hypermethylation and restore normal function of tumor suppressor genes by the use of chromatin-modifying drugs. Decitabine, or 5-aza-2′-deoxycytidine (5-aza-CdR), is a well-characterized drug that is now Food and Drug Administration approved for the treatment of myelodysplastic syndrome. Although 5-aza-CdR is an extremely potent inhibitor of DNA methylation, it is subject to degradation by hydrolytic cleavage and deamination by cytidine deaminase. We show that short oligonucleotides containing a 5-aza-CdR can also inhibit DNA methylation in cancer cells at concentrations comparable with 5-aza-CdR. Detailed studies with S110, a dinucleotide, showed that it works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. Stability of the triazine ring in aqueous solution was not improved in the S110 dinucleotide; however, deamination by cytidine deaminase was dramatically decreased. This is the first demonstration of the use of short oligonucleotides to provide effective delivery and cellular uptake of a nucleotide drug and protection from enzymatic degradation. This approach may pave the way for more stable and potent inhibitors of DNA methylation as well as provide means for improving existing therapeutics. [Cancer Res 2007;67(13):6400–8]
Spontaneous Mammary Tumors Differ Widely in Their Inherent Sensitivity to Adoptively Transferred T Cells
Authors: Wall Erika M. , Milne Katy , Martin Michele L. , Watson Peter H. , Theiss Patty , Nelson Brad H.
Published: July 2007

Immunotherapy of cancer can lead to the selection of antigen loss variants, which provides strong rationale to target oncogenes that are essential for tumor growth or viability. To investigate this concept, we tagged the HER2/neu oncogene with epitopes from ovalbumin to confer recognition by T-cell receptor transgenic CD8+ (OT-I) and CD4+ (OT-II) T cells. Transgenic mice expressing neuOT-I/OT-II developed mammary adenocarcinomas at 6 to 10 months of age. Adoptively transferred naive OT-I cells (with or without OT-II cells) proliferated vigorously on encountering neuOT-I/OT-II-expressing tumors. This was followed by the complete regression of 37% of tumors, whereas others showed partial/stable responses (40%) or progressive disease (23%). Those tumors undergoing complete regression never recurred. In mice with multiple primary tumors, simultaneous regressions and nonregressions were often seen, indicating that immune evasion occurred at a local rather than systemic level. The majority of nonregressing tumors expressed NeuOT-I/OT-II and MHC class I, and many avoided rejection through a profound block to T-cell infiltration. Thus, T cells directed against an essential oncogene can permanently eradicate a subset of spontaneous, established mammary tumors. However, in other tumors, local barriers severely limit the therapeutic response. To maximize the efficacy of immunotherapy against spontaneous cancers, predictive strategies that take into account the heterogeneity of the tumor microenvironment will be required. [Cancer Res 2007;67(13):6442–50]
Positive Cross-Regulatory Loop Ties GATA-3 to Estrogen Receptor α Expression in Breast Cancer
Authors: Eeckhoute Jérôme , Keeton Erika Krasnickas , Lupien Mathieu , Krum Susan A. , Carroll Jason S. , Brown Myles
Published: July 2007

The transcription factor GATA-3 is required for normal mammary gland development, and its expression is highly correlated with estrogen receptor α (ERα) in human breast tumors. However, the functional role of GATA-3 in ERα-positive breast cancers is yet to be established. Here, we show that GATA-3 is required for estradiol stimulation of cell cycle progression in breast cancer cells. The role of GATA-3 in estradiol signaling requires the direct positive regulation of the expression of the ERα gene itself by GATA-3. GATA-3 binds to two cis-regulatory elements located within the ERα gene, and this is required for RNA polymerase II recruitment to ERα promoters. Reciprocally, ERα directly stimulates the transcription of the GATA-3 gene, indicating that these two factors are involved in a positive cross-regulatory loop. Moreover, GATA-3 and ERα regulate their own expression in breast cancer cells. Hence, this transcriptional coregulatory mechanism accounts for the robust coexpression of GATA-3 and ERα in human breast cancers. In addition, these results highlight the crucial role of GATA-3 for the response of ERα-positive breast cancers to estradiol. Moreover, they identify GATA-3 as a critical component of the master cell-type–specific transcriptional network including ERα and FoxA1 that dictates the phenotype of hormone-dependent breast cancer. [Cancer Res 2007;67(13):6477–83]
Effect of Addition of Yohimbine (Alpha-2-Receptor Antagonist) to the Antidepressant Activity of Fluoxetine or Venlafaxine in the Mouse Forced Swim Test
Authors: Dhir Ashish , Kulkarni S.K.
Published: July 2007

Background/Aims: Studies have suggested that α2-adrenoceptors strongly affect monoaminergic neurotransmission by enhancing not only noradrenergic but also serotonergic firing rates. With this background in mind, the present study was undertaken to monitor the effect of addition of yohimbine (α2-adrenoceptor antagonist) to the effect of fluoxetine (selective serotonin reuptake inhibitor) or venlafaxine (dual reuptake inhibitors of both serotonin and norepinephrine) in Porsolt’s forced swim test (FST) using male Laca strain mice. Method: The immobility period was recorded in mouse FST during a 6-min period. Different doses of fluoxetine or venlafaxine were administered 30 min before exposing the animals to the test procedure. In the combination study, yohimbine (2 mg/kg i.p.) was administered 15 min before the administration of different doses of fluoxetine or venlafaxine. Results: Fluoxetine (5, 10, 20 and 40 mg/kg) [F = 28.352] or venlafaxine (2, 4, 8 and 16 mg/kg) [F = 17.842] dose-dependently inhibited the immobility period in mice. Addition of yohimbine (2 mg/kg i.p.) potentiated the antidepressant action of fluoxetine or venlafaxine in mouse FST as the animals showed a decrease in the immobility period compared to the fluoxetine or venlafaxine per se group, respectively. Conclusion: The present study not only demonstrated the association of α2-receptors in the antidepressant effect of fluoxetine or venlafaxine, but also supports its adjuvant therapy with other antidepressant drugs.
Comprehensive Screening of a North American Parkinson’s Disease Cohort for LRRK2 Mutation
Authors: Johnson Janel , Paisán-Ruíz Coro , Lopez Grisel , Crews Cynthia , Britton Angela , Malkani Roniel , Evans E.Whitney , McInerney-Leo Aideen , Jain Shushant , Nussbaum Robert L. , Foote Kelly D. , Mandel Ronald J. , Crawley Anthony , Reimsnider Sharon , Fernandez Hubert H. , Okun Michael S. , Gwinn-Hardy Katrina , Singleton Andrew B.
Published: July 2007

Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson’s disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1–51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.
The Canalith Repositioning Procedure with and without Mastoid Oscillation for the Treatment of Benign Paroxysmal Positional Vertigo
Authors: Ruckenstein Michael J. , Shepard Neil T.
Published: July 2007

Objective: To evaluate the efficacy of mastoid oscillation performed with a canalith repositioning procedure (CRP) for the treatment of benign paroxysmal positional vertigo (BPPV). Study Design: A total of 137 patients with posterior canal BPPV were treated with an Epley CRP with or without mastoid oscillation at a tertiary care, university-based balance center. Data were collected prospectively from all patients via a preprinted diary which they maintained for 14 days after the maneuver. Patients underwent office evaluation at 2 weeks after the maneuver. Results: A total of 137 patients were divided equally between the treatment groups. At 48 h post-treatment, 61% (with vibration) and 64% (without vibration) of patients were free of vertigo. At 2 weeks’ post-treatment, 74% (with vibration) and 85% (without vibration) were vertigo-free. Residual symptoms of lightheadedness/imbalance were experienced by 32% of patients with vibration and 40% of patients without vibration. None of these differences between groups were statistically significant. Conclusion: The addition of mastoid oscillation to the positioning maneuver does not add any therapeutic benefit.
Clinical Heterogeneity among Patients with Obesity Hypoventilation Syndrome: Therapeutic Implications
Authors: Pérez de Llano Luis A. , Golpe Rafael , Ortiz Piquer Montserrat , Veres Racamonde Alejandro , Vázquez Caruncho Manuel , López María J. , Fariñas María Carmen
Published: July 2007

Background: Obesity hypoventilation syndrome (OHS) can be treated with noninvasive positive pressure ventilation (NIPPV). Once clinical stability is achieved, continuous positive airway pressure (CPAP) can be recommended in many cases. However, some patients respond only partially to CPAP and NIPPV is a better option for them. Objectives: To assess treatment effectiveness in 2 groups of patients: those who could be switched to CPAP after polysomnographic titration and those who required NIPPV. Methods: A prospective study of 24 OHS patients was conducted, 11 were treated with CPAP and 13 with NIPPV. Morning and evening arterial blood gases were measured. Daytime and overnight oximetric recordings were performed. A post hoc analysis compared both groups. Results: Neither group exhibited deterioration on morning-to-evening blood gases. All patients in the CPAP group presented SaO2 of less than 90% (CT90%) for <15% of the time on nocturnal and daytime recordings. In the NIPPV group, 8 patients had either daytime or nocturnal CT90% ≧15%. There were no intergroup differences regarding age, body mass index, Epworth scale values or PaO2/PaCO2 prior to treatment. FVC in the NIPPV group was lower than in the CPAP group (p = 0.01). Apnea-hypopnea index was higher (56 ± 23 vs. 36 ± 23, p = 0.049) and baseline CT90% was lower (76 ± 19% vs. 92 ± 14%, p = 0.03) in the CPAP group. Conclusions: Two patient subtypes can be identified. Those controlled with CPAP have better spirometry and a significantly higher apnea-hypopnea index. None of these patients showed daytime hypoxemia and all exhibited satisfactory overnight oxygenation. However, 61% of the NIPPV group had suboptimal oximetry results. Nocturnal/diurnal oximetries should be made to assess treatment efficacy in stable OHS patients who fail to achieve good control with CPAP.
Neutrophil activation via β2 integrins (CD11/CD18): Molecular mechanisms and clinical implications
Authors: Schymeinsky Jürgen , Mócsai Attila , Walzog Barbara
Published: July 2007

Polymorphonuclear neutrophils (PMN) are key components of the innate immunity and their efficient recruitment to the sites of lesion is a prerequisite for acute inflammation. Signaling via adhesion molecules of the β2 integrin family (CD11/CD18) plays an essential role for PMN recruitment and activation during inflammation. In this review, we will focus on the non-receptor tyrosine kinase Syk, an important downstream signaling component of β2 integrins that is required for the control of different PMN functions including adhesion,migration and phagocytosis. The exploration of β2 integrin-mediated Syk activation provided not only novel insights into the control of PMN functions but also led to the identification of Syk as a new molecular target for therapeutic intervention during inflammatory diseases.
A thromboxane A2/prostaglandin H2 receptor antagonist (S18886) shows high antithrombotic efficacy in an experimental model of stent-induced thrombosis
Authors: Vilahur Gemma , Casaní Laura , Badimon Lina
Published: July 2007

Acute thrombosis is a threat in patients undergoing percutaneous coronary intervention with stent implantation. Our objective was to determine if stent-induced thrombus formation could be inhibited by oral treatment with a thromboxane A2/prostaglandin H2 receptor antagonist (TPr; S18886) as an alternative to standard therapy. Pigs were allocated in the following treatment (p.o) groups: I) clopidogrel (CLOP); II) ASA; III) S18886; IV) ASA+CLOP; and V) placebo-control. Damaged vessel was placed in the Badimon chamber containing a stent and perfused at 212/s.Antithrombotic effects were assessed as 111In-platelet deposition (PD) in two series (60 and 180 min after drug intake). Fibrin(ogen) deposition, light transmittance aggregometry (LTA; collagen, U46619, and ADP), and bleeding time (BT) were also evaluated. After 60 min S18886 reduced PD ≤48%, 40%, and 35% vs placebo, CLOP-, and ASA-treated ani mals, respectively (P<0.05), while ASA+CLOP showed a 58% reduction versus placebo (P<0.01).After 3 hours, ASA+CLOP decreased PD by 55%, S18886 by 40%, CLOP alone by 28% (P>0.05), and ASA showed no inhibition versus placebo. Similar effects were found in S18886– and ASA+CLOP-treated animals at both times. Fibrin(ogen) deposition followed the same pattern. Collagen-induced LTA was significantly reduced by ASA, ASA+CLOP, and S18886; S18886 abolished U46619-induced LTA; and, CLOP±ASA reduced ADP-induced LTA in a time-dependent manner. TPr blockade did not prolong BT, whereas CLOP±ASA significantly did (P<0.0001). In conclusion, blockade of theTPr provided a fast and potent platelet inhibitory effect in a porcine model of in-stent thrombosis comparable to that of blocking both the ADP receptor and cyclooxygenase activation; in addition,TPr provided a more favorable bleeding risk profile.
Role of Osteoprotegerin in Arterial Calcification
Authors: Orita Yuichi , Yamamoto Hideya , Kohno Nobuoki , Sugihara Masaaki , Honda Hiroaki , Kawamata Seiichi , Mito Shinji , Soe Nwe Nwe , Yoshizumi Masao
Published: July 2007

Objectives—

Enhanced osteoclastogenesis, increased bone resorption, and osteoporosis have been reported in osteoprotegerin-deficient (OPG (−/−)) mice. OPG (−/−) mice available in Japan usually do not show vascular calcification. We have found that arterial calcification can be quickly induced by a simple procedure in OPG (−/−) mice.

Methods and Results—

Male OPG (−/−), OPG (+/−), and OPG (+/+) mice were fed a high phosphate diet from 6 to 10 weeks after birth, and then 1α,25-dihydroxyvitamin D3 (calcitriol) was injected for 3 days. We found that severe calcification developed in the media of the aorta in OPG (−/−) mice. Under electron microscopy, calcium deposits were observed in the cytoplasm and extracellular matrix of vascular smooth muscle cells (VSMCs). Neither apoptosis of VSMCs nor infiltration of macrophages was observed. Alkaline phosphatase (ALP) activity of aortic tissue correlated with the calcified lesion area. Mouse aorta and bone extracts revealed an identical pattern by ALP electrophoresis.

Conclusions—

Our results demonstrated that OPG had anticalcification activity in the aorta, probably through the downregulation of ALP activity. Because the time course of arterial calcification after the injection of calcitriol is accurate and reproducible, this mouse model will be useful for further investigation of vascular calcification.
Cardiac Transgenic and Gene Transfer Strategies Converge to Support an Important Role for Troponin I in Regulating Relaxation in Cardiac Myocytes
Authors: Yasuda So-ichiro , Coutu Pierre , Sadayappan Sakthivel , Robbins Jeffrey , Metzger Joseph M.
Published: July 2007

Elucidating the relative roles of cardiac troponin I (cTnI) and phospholamban (PLN) in β-adrenergic–mediated hastening of cardiac relaxation has been challenging and controversial. To test the hypothesis that β-adrenergic phosphorylation of cTnI has a prominent role in accelerating cardiac myocyte relaxation performance we used transgenic (Tg) mice bearing near complete replacement of native cTnI with a β-adrenergic phospho-mimetic of cTnI whereby tandem serine codons 23/24 were converted to aspartic acids (cTnI S23/24D). Adult cardiac myocytes were isolated and contractility determined at physiological temperature under unloaded and loaded conditions using micro-carbon fibers. At baseline, cTnI S23/24D myocytes had significantly faster relaxation times relative to controls, and isoproterenol stimulation (Iso) had only a small effect to further speed relaxation in cTnI S23/24D myocytes (delta Iso: 7.2 ms) relative to the maximum Iso effect (31.2 ms) in control. The Ca
2+
transient decay rate was similarly accelerated by Iso in Tg and nontransgenic (Ntg) myocytes. Gene transfer of cTnI S23/24D to myocytes in primary culture showed comparable findings. Gene transfer of cTnI with both serines 23/24 converted to alanines (cTnI S23/24A), or gene transfer of slow skeletal TnI, both of which lack PKA phosphorylation sites, significantly blunted Iso-mediated enhanced relaxation compared with controls. Gene transfer of wild-type cTnI had no effect on relaxation. These findings support a key role of cTnI in myocyte relaxation and highlight a direct contribution of the myofilaments in modulating the dynamics of myocardial performance.
Plaque Rupture in the Carotid Artery Is Localized at the High Shear Stress Region
Authors: Groen Harald C. , Gijsen Frank J.H. , van der Lugt Aad , Ferguson Marina S. , Hatsukami Thomas S. , van der Steen Anton F.W. , Yuan Chun , Wentzel Jolanda J.
Published: July 2007

Background and Purpose—

Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS.

Summary of Case—

We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location.

Conclusions—

In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events.
Rabbi Hayyim of Volozhin's Non-Messianic Vision of the Present and Future
Authors: Shapiro Harvey
Published: July 2007

Recent studies have characterized R. Hayyim of Volozhin (1749–1821) as actively preparing for the messianic redemption. Contrary to this, I maintain that R. Hayyim was concerned with the immediate potential of the world in the context of historical time (divre ha-yamim), rather than with a world-to-come, in the context of messianic time (aharit ha-yamim). To R. Hayyim, the existence of the cosmos and the stability of a dynamic life-giving universe are fraught with contingency because of the interdependent organic naturality shared by man and world. This contingency is constant, placing man's conduct as the central determinant of the world's future. R. Hayyim's theory and practice attest to a concern for the immanent and transcendent aspects of this world and for the meanings of our everyday experienced relationship to its variegated pragmata.
Female Recidivists Speak About Their Experience in Drug Court While Engaging in Appreciative Inquiry
Authors: Fischer Michael , Geiger Brenda , Hughes Mary Ellen
Published: July 2007

Eleven female drug-court participants looked at current and past experiences to assess their program and envision future program innovations. From these women's perspective, the strongest component of drug court was being surrounded by staff dedicated to their progress and recovery. Graduated supervision and accurate drug testing were appreciated rather than resented when the participants were not humiliated and were treated with respect. Wraparound services, resources, and referral; treatment facilities that accepted children; and individualized treatment plans and therapy with offenders who are ex-addicts, and preferably females, allowed for greater involvement and active participation in recovery. Progressing through three phases, acquiring skills, a job, and visitation rights to see their children or regaining custody, increased these women's sense of self-efficacy perception and confidence in their ability to lead a drug-free, meaningful life. Findings show the importance of qualitative criteria in evaluating drug-court participants' progress and the process of recovery.
The Effect of Inmates' Self-Reported Childhood and Adolescent Animal Cruelty
Authors: Hensley Christopher , Tallichet Suzanne E.
Published: July 2007

Few researchers have investigated the potentially predictive power of motives for childhood and adolescent animal cruelty as it is associated with interpersonal violence in adulthood. Based on a sample of 261 inmates at medium- and maximum-security prisons in a southern state, the present study examines the relationship among several retrospectively reported motives (anger, fun, dislike, and imitation) for animal cruelty and violent crime convictions (assault, rape, and murder). Almost half reported abusing animals out of anger, whereas more than one third did so for fun. Dislike for the animal and imitation were less frequently occurring motives. Participants who abused animals at an earlier age and those who did so out of anger or for fun were more likely to repeat the offense. Regression analyses revealed that abusing an animal out of fun in their youth was the most statistically salient motive for predicting later interpersonal violence as adults.
Selection Bias and Peer Effects in Team Sports
Authors: Ashworth John , Heyndels Bruno
Published: July 2007

This article analyzes how age grouping in youth competitions and soccer education programs affects wage formation at the professional level. A simple theoretical model shows that professional players born late after the cutoff date are expected to earn systematically higher wages than their early-born peers. Two discriminating factors are responsible for this: a systematic bias in the talent detection system and peer effects in the production process of human (sports) capital. The authors demonstrate the existence of such an effect among (native) German professional soccer players. Estimating an earnings function for players in the 1997-1998 and 1998-1999 seasons, the authors find clear evidence of a month-of-birth-related wage bias. Players born late after the cutoff date earn systematically higher wages, though this effect is not discernible in all positions; it is strongest for goalkeepers and defenders but not evident for forwards.
The heritage of early FC in document reference retrieval systems, 1920–1969
Authors: La Barre Kathryn
Published: July 2007

Revisits the heritage of faceted classification (FC) beginning with an examination of the Universal Decimal Classification (UDC) in its early manifestations and the groundwork established by international documentalist groups. Early document retrieval experimentation with FC during the intensive period of system design, testing and evaluation in the 1950s and 1960s is discussed, as well as the rise of an international discourse community that sought to augment and extend the reach of FC through system implementations. A list of acronyms employed in the article is given in an appendix.
Serial personal digital assistant data capture of health-related quality of life: A randomized controlled trial in a prostate cancer clinic
Authors: Matthew Andrew G , Currie Kristen L , Irvine Jane , Ritvo Paul , Santa Mina Daniel , Jamnicky Leah , Nam Robert , Trachtenberg John
Published: July 2007

Background

In clinical and research practice linked to prostate cancer treatment, frequent monitoring of patient health-related quality of life (HRQOL) is essential. Practical and analytic limitations of paper questionnaire data capture may be overcome with the use of self-administered personal digital assistant (PDA) data collection. The objective of this study was to assess the reliability, validity, and feasibility of using PDA in place of paper versions of the International Prostate Symptom Score (IPSS), the Patient Oriented Prostate Cancer Utility Survey (PORPUS), and the International Index of Erectile Function-5 (IIEF-5) in a prostate cancer clinic setting.

Methods

152 participants were randomly assigned to one of three conditions: 1) paper followed by PDA survey; 2) PDA followed by paper survey; or 3) PDA followed by PDA survey. Evaluation included an assessment of data quality (internal consistency, test-retest reliability, response correlation, completeness of data), and feasibility (participation rates, time to completion, preference and difficultly/ease of using PDA).

Results

Internal consistency was similar for both PDA and paper applications. Test-retest reliability was confirmed for PDA repeated administration. Data from paper and PDA questionnaires were strongly correlated. Lower missed item rates were found in PDA administration. 82.8% of participants preferred using the PDA or had no preference. Mean difficulty/ease ratings indicated that participants found the PDA easy to use. Age did not significantly correlate with preference or difficulty.

Conclusion

The results confirm the adaptability of the IPSS, IIEF-5, and the PORPUS to PDA administration. Similarly, the findings of this study support the feasibility of using PDA technology for HRQOL serial data capture in the prostate cancer patient population.
Identification of 9 uterine genes that are regulated during mouse pregnancy and exhibit abnormal levels in the cyclooxygenase-1 knockout mouse
Authors: Zhao Baohui , Koon Deanna , Curtis Allyson L , Soper Jessica , Bethin Kathleen E
Published: July 2007

Background

Preterm birth is the leading cause of all infant mortality. In 2004, 12.5% of all births were preterm. In order to understand preterm labor, we must first understand normal labor. Since many of the myometrial changes that occur during pregnancy are similar in mice and humans and mouse gestation is short, we have studied the uterine genes that change in the mouse during pregnancy. Here, we used microarray analysis to identify uterine genes in the gravid mouse that are differentially regulated in the cyclooxygenase-1 knockout mouse model of delayed parturition.

Methods

Gestational d18.0 uteri (n = 4) were collected from pregnant wild-type and cyclooxygenase-1 knockout mice. Part of the uterus was used for frozen sections and RNA was isolated from the remainder. Microarray analysis was performed at the Indiana University School of Medicine Genomic Core and analyzed using the Microarray Data Portal. Northern analysis was performed to confirm microarray data and the genes localized in the gravid uterus by in situ hybridization.

Results

We identified 277 genes that are abnormally expressed in the gravid d18.0 cyclooxygenase-1 knockout mouse. Nine of these genes are also regulated in the normal murine uterus during the last half of gestation. Many of these genes are involved in the immune response, consistent with an important role of the immune system in parturition. Expression of 4 of these genes; arginase I, IgJ, Tnfrsf9 and troponin; was confirmed by Northern analysis to be mis-regulated during pregnancy in the knockout mouse. In situ hybridization of these genes demonstrated a similar location in the gravid wild-type and Cox-1 knockout mouse uteri.

Conclusion

To our knowledge, this is the first work to demonstrate the uterine location of these 4 genes in the mouse during late pregnancy. There are several putative transcription factor binding sites that are shared by many of the 9 genes identified here including; estrogen and progesterone response elements and Ets binding sites. In summary, this work identifies 9 uterine murine genes that may play a role in parturition. The function of these genes is consistent with an important role of the immune system in parturition.
Geographic variation and localised clustering of congenital anomalies in Great Britain
Authors: Armstrong Ben G , Dolk Helen , Pattenden Sam , Vrijheid Martine , Loane Maria , Rankin Judith , Dunn Chris E , Grundy Chris , Abramsky Lenore , Boyd Patricia A , Stone David , Wellesley Diana
Published: July 2007

Background

Environmental pollution as a cause of congenital anomalies is sometimes suspected because of clustering of anomalies in areas of higher exposure. This highlights questions around spatial heterogeneity (clustering) in congenital anomaly rates. If spatial variation is endemic, then any one specific cluster is less remarkable, though the presence of uncontrolled geographically clustered risk factors is suggested. If rates are relatively homogeneous across space other than around specific hazards, then evidence for these hazards causing the clusters is strengthened. We sought to estimate the extent of spatial heterogeneity in congenital anomaly rates in the United Kingdom.

Methods

The study population covered about one million births from five registers in Britain from 1991–1999. We estimated heterogeneity across four geographical levels: register area, hospital catchment, electoral ward, and enumeration district, using a negative binomial regression model. We also sought clusters using a circular scan statistic.

Results

Congenital anomaly rates clearly varied across register areas and hospital catchments (p < 0.001), but not below this level (p > 0.2). Adjusting for socioeconomic deprivation and maternal age made little difference to the extent of geographical variation for most congenital anomaly subtypes. The two most significant circular clusters (of four ano-rectal atresias and six congenital heart diseases) contained two or more siblings.

Conclusion

The variation in rates between registers and hospital catchment area may have resulted in part from differences in case ascertainment, and this should be taken into account in geographical epidemiological studies of environmental exposures. The absence of evidence for variation below this level should be interpreted cautiously in view of the low power of general heterogeneity tests. Nevertheless, the data suggest that strong localised clusters in congenital anomalies are uncommon, so clusters around specific putative environmental hazards are remarkable when observed. Negative binomial models applied at successive hierarchical levels provide an approach of intermediate complexity to characterising geographical heterogeneity.
Improving the virtual source method by wavefield separation
Authors: Mehta Kurang , Bakulin Andrey , Sheiman Jonathan , Calvert Rodney , Snieder Roel
Published: July 2007

The virtual source method has recently been proposed to image and monitor below complex and time-varying overburden. The method requires surface shooting recorded at downhole receivers placed below the distorting or changing part of the overburden. Redatuming with the measured Green’s function allows the reconstruction of a complete downhole survey as if the sources were also buried at the receiver locations. There are still some challenges that need to be addressed in the virtual source method, such as limited acquisition aperture and energy coming from the overburden. We demonstrate that up-down wavefield separation can substantially improve the quality of virtual source data. First, it allows us to eliminate artifacts associated with the limited acquisition aperture typically used in practice. Second, it allows us to reconstruct a new optimized response in the absence of downgoing reflections and multiples from the overburden. These improvements are illustrated on a synthetic data set of a complex layered model modeled after the Fahud field in Oman, and on ocean-bottom seismic data acquired in the Mars field in the deepwater Gulf of Mexico.
Time-lapse ERT monitoring of an injection/withdrawal experiment in a shallow unconfined aquifer
Authors: Oldenborger Greg A. , Knoll Michael D. , Routh Partha S. , LaBrecque Douglas J.
Published: July 2007

To quantify performance of 3D time-lapse electrical resistivity tomography (ERT), a sequential injection/withdrawal experiment was designed for monitoring the pump-and-capture remediation of a conductive solute in an unconfined alluvial aquifer. Prior information is incorporated into the inversion procedure via regularization with respect to a reference model according to three protocols: (1) independent regularization involving a single reference model, (2) background regularization involving a reference model obtained via inversion of preinjection data, and (3) time-lapse regularization involving an evolving reference model obtained via inversion of data from previous experimental stages. Emplacement and sequential withdrawal of the solute is clearly imaged for all protocols. Time-lapse regularization results in greater amounts of model structure, while providing signifi-cant computational savings. ERT-estimated electrical conductivity is used to predict solute concentration and solute mass in the aquifer. At any experimental stage, we are able to estimate total solute mass in the aquifer with a maximum accuracy of 60%–85% depending on regularization protocol and survey geometry. We also estimate the withdrawn solute mass for every experimental stage (the change in mass between experimental stages). Withdrawn mass estimates are more reliable than total mass estimates and do not exhibit systematic underprediction or dependence on regularization protocol. Withdrawn mass estimates are accurate for changes in mass below [Formula: see text] of potassium bromide [Formula: see text] for horizontal and vertical dipole-dipole surveys, respectively. Estimating the withdrawn solute mass does not require background subtraction and, thus, does not require background data.
Forward modeling of fracture-induced sonic anisotropy using a combination of borehole image and sonic logs
Authors: Prioul Romain , Donald Adam , Koepsell Randy , Marzouki Zakariae El , Bratton Tom
Published: July 2007

We develop a methodology to model and interpret borehole dipole sonic anisotropy related to the effect of geologic fractures, using a forward-modeling approach. We use a classical excess-compliance fracture model that relies on the orientation of the individual fractures, the elastic properties of the host rock, and the normal and tangential fracture-compliance parameters. Orientations of individual fractures are extracted from borehole-image log analysis. The model is validated using borehole-resistivity image and sonic logs in a gas-sand reservoir over a [Formula: see text] (50 m) vertical interval of a well. Significant amounts of sonic anisotropy are observed at three zones, with a fast-shear azimuth (FSA) exhibiting 60° of variation and slowness difference between 2% and 16%. Numerous quasivertical fractures with varying dip azimuths are identified on the image log at the locations of strong sonic anisotropy. The maximum horizontal-stress direction, given by breakouts and drilling-induced fractures, is shown not to be aligned with the strike of natural fractures. We show that using just two adjustable fracture-compliance parameters, one fornatural fractures and one for drilling-induced fractures, is an excel-lent first-order approximation to explain the fracture-induced anisotropy response over a depth interval of [Formula: see text]. Given the presence of gas and the absence of clay filling within the fractures, we assumed equal normal and tangential compliances. The two inverted normal compliances are [Formula: see text] and [Formula: see text]. Predicted FSA matches measured FSA over [Formula: see text] (40 m) of the [Formula: see text] (50 m) studied interval. Predicted slowness anisotropy matches the overall variation and measured values of anisotropy for two of the three strong anisotropy zones. Analysis of the symmetries of the modeled anisotropic response shows that the medium is mostly a horizontal transverse isotropic medium, with small azimuthal variation of the symmetry axis. Analysis of each independent fracture type shows that the anisotropy is mainly driven by open or partially healed fractures, but also consistent with stress-related, drilling-induced fractures. Therefore, the measured sonic anisotropy is caused by the combination of stress and fracture effects where the predominance of one mechanism over the other is depth-dependent. This method provides a consistent approach to data interpretation by integrating borehole image and sonic logs that probe the formation at different depths of investigation around the borehole.
Sonic logging in deviated boreholes penetrating an anisotropic formation: Laboratory study
Authors: Zhu Zhenya , Chi Shihong , Toksöz M. Nafi
Published: July 2007

Development of deepwater fields requires drilling deviated or horizontal wells. Many formations are highly anisotropic, that is, the P- and S-wave velocities vary with propagation direction. Sonic logs acquired in these wells need to be corrected for anisotropy effects before the logs can be used in formation evaluation and seismic applications. In this study, we use a laboratory model made of an orthorhombic Phenolite block to study acoustic logging in deviated wells. We first measure the qP-, qSV-, and SH-wave group velocities by using body waves at angles of 0°, 15°, 30°, 45°, 60°, 75°, and 90° relative to the slowest P-wave principal axis of the Phenolite block. We then drill holes at the same angles in the block. We record monopole and dipole sonic waveforms in these holes and extract the qP-, qSV-, SH-, and Stoneley-wave velocities by using the slowness-time semblance method. The velocities measured through the use of monopole logging and dipole logging vary with borehole deviations. We find that an equivalent transversely isotropic (TI) model can fit the measured qP-, qSV-, and Stoneley-wave velocities very well. The S-wave velocities at low to medium borehole deviations can be used to differentiate an orthorhombic material from a TI one.
Zero-offset seismic amplitude decomposition and migration
Authors: Ursin Bjørn , Tygel Martin
Published: July 2007

In an anisotropic medium, a normal-incidence wave is multiply transmitted and reflected down to a reflector where the phase-velocity vector is parallel to the interface normal. The ray code of the upgoing wave is equal to the ray code of the downgoing wave in reverse order. The geometric spreading, KMAH index, and transmission and reflection coefficients of the normal-incidence ray can be expressed in terms of products or sums of the corresponding quantities of the one-way normal and normal-incidence-point (NIP) waves. Here, we show that the amplitude of the ray-theoretic Green’s function for the reflected wave also follows a similar decomposition in terms of the amplitude of the Green’s function of the NIP wave and the normal wave. We use this property to propose three schemes for true-amplitude poststack depth migration in anisotropic media where the image represents an estimate of the zero-offset reflection coefficient. The first is a map migration procedure in which selected primary zero-offset reflections are converted into depth with attached true amplitudes. The second is a ray-based, Kirchhoff-type full migration. The third is a wave equation continuation algorithm to reverse-propagate the recorded wavefield in a half-velocity model with half the elastic constants and double the density. The image is formed by taking the reverse-propagated wavefield at time equal to zero followed by a geometric spreading correction.
Management of Ovarian Germ Cell Tumors
Authors: Gershenson David M.
Published: July 2007

Purpose

To review contemporary management of malignant ovarian germ cell tumors (MOGCT).

Design

The literature on the topic of MOGCT is reviewed, including pathology, prognostic factors, surgical strategies, postoperative therapy, late effects of therapy, and treatment of recurrence.

Results

Prognostic factors for MOGCT include the International Federation of Gynecology and Obstetrics staging system's stage, residual disease, histologic type, and elevation of serum tumor markers. Fertility-sparing surgery is possible in a large proportion of patients. The importance of comprehensive surgical staging is somewhat controversial. For patients with advanced-stage disease, maximum cytoreductive surgery appears to be beneficial. Although second-look surgery is not recommended routinely, selected patients may benefit from secondary cytoreduction. For those patients who require postoperative chemotherapy, standard therapy consists of the combination of bleomycin, etoposide, and cisplatin. However, there is a growing trend toward surveillance; this strategy continues to be studied. Although premature menopause may occur in a small proportion of patients, at least 80% of those who undergo fertility-sparing surgery and chemotherapy may expect to preserve reproductive function. For patients with early-stage disease, cure rates approach 100%. For those with advanced-stage disease, cure rates are reportedly at least 75%.

Conclusion

MOGCT is a rare malignancy that principally affects girls and young women. With optimal therapy, the prognosis is excellent, and most patients may retain reproductive function.
Type B γ-Aminobutyric Acid Receptors Modulate the Function of the Extracellular Ca2+-Sensing Receptor and Cell Differentiation in Murine Growth Plate Chondrocytes
Authors: Cheng Zhiqiang , Tu Chialing , Rodriguez Luis , Chen Tsui-Hua , Dvorak Melita M. , Margeta Marta , Gassmann Martin , Bettler Bernhard , Shoback Dolores , Chang Wenhan
Published: July 2007

Extracellular calcium-sensing receptors (CaRs) and metabotropic or type B γ-aminobutyric acid receptors (GABA-B-Rs), two closely related members of family C of the G protein-coupled receptor superfamily, dimerize in the formation of signaling and membrane-anchored receptor complexes. We tested whether CaRs and two GABA-B-R subunits (R1 and R2) are expressed in mouse growth plate chondrocytes (GPCs) by PCR and immunocytochemistry and whether interactions between these receptors influence the expression and function of the CaR and extracellular Ca2+-mediated cell differentiation. Both CaRs and the GABA-B-R1 and -R2 were expressed in the same zones of the growth plate and extensively colocalized in intracellular compartments and on the membranes of cultured GPCs. The GABA-B-R1 coimmunoprecipitated with the CaR, confirming a physical interaction between the two receptors in GPCs. In vitro knockout of GABA-B-R1 genes, using a Cre-lox recombination strategy, blunted the ability of high extracellular Ca2+ concentration to activate phospholipase C and ERK1/2, suppressed cell proliferation, and enhanced apoptosis in cultured GPCs. In GPCs, in which the GABA-B-R1 was acutely knocked down, there was reduced expression of early chondrocyte markers, aggrecan and type II collagen, and increased expression of the late differentiation markers, type X collagen and osteopontin. These results support the idea that physical interactions between CaRs and GABA-B-R1s modulate the growth and differentiation of GPCs, potentially by altering the function of CaRs.
Location and habitat characteristics of the breeding nests of the harvest mouse (Micromys minutus) in the reed-beds of an intensively used farmland
Authors: Surmacki Adrian , Gołdyn Bartłomiej , Tryjanowski Piotr
Published: July 2007

Occurrence of harvest mouse breeding nests in relation to reed-bed structure
was studied in 2000-2001. This study took place in midfield marsh patches
and drainage ditches in an intensively used farmland of western Poland.
A total of 88 nests was found. 98% of them were attached to reed stems at a
mean height of 48 (± 41 SD) cm. Harvest mice favoured reed-beds with low,
thin and sparse stalks, with a high ratio of Carex/grass. Areas with a high
density of herbaceous vegetation were avoided as nest sites.