bluuebunny/crossref_metadata_2025 huggingface dataset:
The Quality of Media Reports on Discoveries Related to Human Genetic Diseases
Authors: Holtzman Neil A. , Bernhardt Barbara A. , Mountcastle-Shah Eliza , Rodgers Joann E. , Tambor Ellen , Geller Gail
Published: August 2005

Objectives: To examine (1) the quality of media reports (newspapers, television and public radio) of genetic discoveries with medical relevance and (2) factors related to the completeness and balance of the stories. Methods: Analysis of the accuracy, balance, and completeness of 228 media stories reporting 24 genetic discoveries between 1996 and 2000 using a previously validated instrument. Results: Although usually accurate, the stories contained only 45.5 ± 13.8% (mean ± SD) of relevant items. Stories appearing on television and stories reporting discoveries of genes for rare diseases were the least complete. Stories in non-US English-speaking newspapers included more content items per word than US stories. Less balanced stories exaggerated the benefits of discoveries, ignored possible risks, and did not present a range of expert opinion. Scientists were sometimes the source of exaggeration. Conclusions: To increase the quality of media reports about genetic discoveries, stories should include more relevant items and be written by journalists skilled in science writing. Scientists will have to resist the tendency to exaggerate. These conclusions may apply to media stories of other discoveries as well.
Prenatal Diagnosis and Managementof Fetal Xerocytosis Associated with Ascites
Authors: Sánchez Myriam , Palacio Montse , Borrell Antoni , Carmona Francesc , Cobo Teresa , Coll Oriol , Cararach Vicenç
Published: August 2005

Objectives: To discuss the prenatal diagnosis and management of fetal xerocytosis associated with ascites. Case Report: A 29-year-old woman with hereditary xerocytosis was found to present a fetus with severe ascites on the 20-week scan. Cordocentesis showed mild anemia and blood transfusion was discarded. Ascites worsened and 2 weeks later a new cordocentesis showed lower hematocrit values. Blood transfusion was performed but ascites remained unchanged. Cordocentesis was repeated at 28 weeks and albumin was transfused. Fetal hemoglobin was within the normal range. Peak systolic velocity of the middle cerebral artery remained normal and correctly predicted mild anemia. Expectant management was followed. An elective cesarean section was performed at 32 weeks because of breech presentation and preterm labor which did not respond to aggressive tocolysis. A female newborn weighing 2,615 g was delivered and required paracenteses and exchange transfusion. The newborn was discharged at 4 weeks of life and at 2 months of age, the ascites resolved completely. Conclusions: The mechanism of development of ascites in fetal xerocytosis remains unanswered. As ascites does not seem to be related to fetal anemia or hypoalbuminemia, does not substantially change after blood transfusion and tends to resolve in late gestation, a conservative management is reasonable if fetal anemia is not severe.
Coelomic Fluid Leptin Concentration in Normal First-Trimester Pregnancies and Missed Miscarriages
Authors: Makrydimas G. , Vandecruys H. , Sotiriadis A. , Lakasing L. , Spencer K. , Nicolaides K.H.
Published: August 2005

Objective: Investigation of the possible role of leptin in early pregnancy failure. Methods: Leptin concentration was measured in maternal serum, coelomic fluid and amniotic fluid from 15 singleton pregnancies with live fetuses and 7 missed miscarriages at 7–10 weeks of gestation. Results: In the pregnancies with live fetuses, the median leptin concentration was significantly higher in coelomic fluid (median 33.1 ng/ml) than in maternal serum (median 8.1 ng/ml) or amniotic fluid (median 0.5 ng/ml). In the pregnancies with missed miscarriage, compared to those with live fetuses, the median leptin concentration in coelomic fluid was higher (median 45.3 ng/ml), but in maternal serum it was not significantly different (median 5.5 ng/ml). Conclusions: The high coelomic fluid leptin concentration suggests that embryonic death may be preceded by impaired oxygenation of the placenta that stimulates production of leptin.
Associations Between Soluble CD40 Ligand, Atherosclerosis Risk Factors, and Subclinical Atherosclerosis
Authors: de Lemos James A. , Zirlik Andreas , Schönbeck Uwe , Varo Nerea , Murphy Sabina A. , Khera Amit , McGuire Darren K. , Stanek Greg , Lo Hao S. , Nuzzo Rebecca , Morrow David A. , Peshock Ronald , Libby Peter
Published: August 2005

Objectives—

The purpose of this study was to evaluate the associations between plasma levels of soluble CD40 ligand (sCD40L), atherosclerosis risk factors, and evidence of subclinical atherosclerosis.

Methods and Results—

Plasma levels of sCD40L were measured in 2811 subjects from the Dallas Heart Study, a multiethnic population-based cross-sectional study. Electron Beam Computed Tomography measurements of coronary artery calcium (CAC) and MRI measurements of aortic plaque were performed in 2198 and 1965 subjects, respectively. No association was observed between quartiles of sCD40L and age, sex, race, body mass index, diabetes, smoking, creatinine clearance, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or C-reactive protein. In contrast, weak but statistically significant associations were observed between sCD40L and total cholesterol and triglycerides. The prevalence of detectable CAC (CAC score ≥10) and aortic plaque did not differ across sCD40L quartiles, and individuals with CAC scores <10, ≥10 to 100, >100 to 400, and >400 had similar sCD40L levels.

Conclusions—

In a large and representative multiethnic population-based sample, sCD40L was not associated with most atherosclerotic risk factors or with subclinical atherosclerosis. These findings suggest that sCD40L will not be useful as a tool to screen for the presence of subclinical atherosclerosis in the population. Further evaluation of this biomarker should focus on settings in which platelet activation is common, such as following acute coronary syndromes or coronary revascularization procedures.
Devotion and Domesticity: The Reconfiguration of Gender in Popular Christian Pamphlets from Ghana and Nigeria
Authors: Newell Stephanie
Published: August 2005

Drawing upon interviews with readers in Ghana and Nigeria as well as a large number of locally published marriage guidance pamphlets, this article considers attitudes toward the printed word among Christian readers in West Africa. Gender is an especially significant category in West African 'how-to' books, particularly those produced by Pentecostal and evangelical authors. While the majority of male authors try to reinstate Pauline strictures on wifely submission in their writing, the female authors discussed in this article make use of biblical quotation alongside romantic discourse in order to reconfigure both men's and women's marital roles. In so doing, they construct marital utopias which reveal a great deal about the contradictions and paradoxes of contemporary Christian gender ideologies in West Africa.
Simultaneous Measurement of Ocean Winds and Waves with an Airborne Coherent Real Aperture Radar
Authors: Plant William J. , Keller William C. , Hayes Kenneth
Published: August 2005

A coherent, X-band airborne radar has been developed to measure wind speed and direction simultaneously with directional wave spectra on the ocean. The coherent real aperture radar (CORAR) measures received power, mean Doppler shifts, and mean Doppler bandwidths from small-resolution cells on the ocean surface and converts them into measurements of winds and waves. The system operates with two sets of antennas, one rotating and one looking to the side of the airplane. The rotating antennas yield neutral wind vectors at a height of 10 m above the ocean surface using a scatterometer model function to relate measured cross sections to wind speed and direction. The side-looking antennas produce maps of normalized radar cross section and line-of-sight velocity from which directional ocean wave spectra may be obtained. Capabilities of CORAR for wind and wave measurement are illustrated using data taken during the Shoaling Waves Experiment (SHOWEX) sponsored by the Office of Naval Research. Wind vectors measured by CORAR agree well with those measured by nearby buoys. Directional wave spectra obtained by CORAR also agree with buoy measurements and illustrate that offshore winds can produce dominant waves at an angle to the wind vector that are in good agreement with the measurements. The best agreement is produced using the Joint North Sea Wave Project (JONSWAP) parameterizations of the development of wave height and period with fetch.
Infrared Interferometric Measurements of the Near-Surface Air Temperature over the Oceans
Authors: Minnett P. J. , Maillet K. A. , Hanafin J. A. , Osborne B. J.
Published: August 2005

The radiometric measurement of the marine air temperature using a Fourier transform infrared spectroradiometer is described. The measurements are taken by the Marine-Atmospheric Emitted Radiance Interferometer (M-AERI) that has been deployed on many research ships in a wide range of conditions. This approach is inherently more accurate than conventional techniques and can be used to determine some of the error characteristics of the standard measurements. Examples are given from several cruises ranging from the Arctic to the equatorial Pacific Oceans. It is shown that the diurnal heating signal in radiometric air temperatures in the tropical Pacific can typically reach an amplitude of ∼15% of that measured by conventional sensors. Conventional data have long been recognized as being contaminated by direct solar heating and heat island effects of the ships or buoys on which they are mounted, but here this effect is quantified by comparisons with radiometric measurements.
Response Functions for Arbitrary Weight Functions and Data Distributions. Part I: Framework for Interpreting the Response Function
Authors: Askelson Mark A. , Straka Jerry M.
Published: August 2005

The response function is a commonly used measure of analysis scheme properties. Its use in the interpretation of analyses of real-valued data, however, is unnecessarily complicated by the structure of the standard form of the Fourier transform. Specifically, interpretation using this form of the Fourier transform requires knowledge of the relationship between Fourier transform values that are symmetric about the origin. Here, these relationships are used to simplify the application of the response function to the interpretation of analysis scheme properties.

In doing so, Fourier transforms are used because they can be applied to studying effects that both data sampling and weight functions have upon analyses. A complication arises, however, in the treatment of constant and sinusoidal input since they do not have Fourier transforms in the traditional sense. To handle these highly useful forms, distribution theory is used to generalize Fourier transform theory. This extension enables Fourier transform theory to handle both functions that have Fourier transforms in the traditional sense and functions that can be represented using Fourier series.

The key step in simplifying the use of the response function is the expression of the inverse Fourier transform in a magnitude and phase form, which involves folding the integration domain onto itself so that integration is performed over only half of the domain. Once this is accomplished, interpretation of the response function is in terms of amplitude and phase modulations, which indicate how amplitudes and phases of input waves are affected by an analysis scheme. This interpretation is quite elegant since its formulation in terms of properties of input waves results in a one-to-one input-to-output wave interpretation of analysis scheme effects.
Influences of a Winter Wheat Belt on the Evolution of the Boundary Layer
Authors: McPherson Renee A. , Stensrud David J.
Published: August 2005

Evidence exists that a large-scale alteration of land use by humans can cause changes in the climatology of the region. The largest-scale transformation is the substitution of native landscape by agricultural cropland. This modeling study examines the impact of a direct substitution of one type of grassland for another—in this case, the replacement of tallgrass prairie with winter wheat. The primary difference between these grasses is their growing season: native prairie grasses of the U.S. Great Plains are warm-season grasses whereas winter wheat is a cool-season grass.

Case study simulations were conducted for 27 March 2000 and 5 April 2000—days analyzed in previous observational studies. The simulations provided additional insight into the physical processes involved and changes that occurred throughout the depth of the planetary boundary layer. Results indicate the following: 1) with the proper adjustment of vegetation parameters, land-use type, fractional vegetation coverage, and soil moisture, the numerical simulations were able to capture the overall patterns measured near the surface across a growing wheat belt during benign springtime conditions in Oklahoma; 2) the impacts of the mesoscale belt of growing wheat included increased values of latent heat flux and decreased values of sensible heat flux over the wheat, increased values of atmospheric moisture near the surface above and downstream of the wheat, and a shallower planetary boundary layer (PBL) above and downstream of the wheat; 3) in the sheared environments that were examined, a shallower PBL that resulted from growing wheat (rather than natural vegetation) led to reduced entrainment of higher momentum air into the PBL and, thus, weaker winds within the PBL over and downwind from the growing wheat; 4) for the cases studied, gradients in sensible heat were insufficient to establish an unambiguous vegetation breeze or its corresponding mesoscale circulation; 5) the initialization of soil moisture within the root zone aided latent heat fluxes from growing vegetation; and 6) reasonable specification of land surface parameters was required for the correct simulation and prediction of surface heat fluxes and resulting boundary layer development.
The Process of Bricolage Between Mythic Societies and Global Modernity: Conversion to the Assembly of God Faith in Burkina Faso
Authors: Laurent Pierre-Joseph
Published: August 2005

English

The case of conversions in Assembly of God churches in Burkina Faso is typical of the identity tinkering which is now going on in West African societies. Through individual conversion experiences, this particular variant of Christianity ends up playing the role of the group that makes one leave one's original group. Conversion thus constitutes a break which allows one to dare to transgress normal boundaries. In the context of a modernity beset by unaccustomed fears and doubts, religious allegiances often prove to be complex acts of identity bricolage,1 which even involve a second level of construction, that of an identity which is specifically constructed to defend me against another who is persecuting me.

French

Les conversions aux Assemblées de Dieu du Burkina Faso sont emblématiques du bricolage identitaire en train de se faire dans les sociétés d'Afrique de l'Ouest. A travers ces expériences de conversion individuelle, cette forme particuliè re de christianisme joue le rôle de groupe de la sortie du groupe coutumier. La conversion constitue ainsi une rupture permettant d'oser transgresser. En contexte de modernité insécurisée, les appartenances religieuses s'avèrent dès lors des bricolages complexes, révélant en creux un second niveau de bricolage, celui d'une identité fac¸ onnée pour se préserver d'une autre perc¸ ue comme persécutrice.
Russian revolutionaries and English sympathizers in 1890s London
Authors: Vernitski Anat
Published: August 2005

The topic of this paper is a unique Anglo-Russian intellectual and emotional exchange that developed in late Victorian London. The paper analyses the way political, cultural and personal aspects of this Anglo-Russian circle intertwined and influenced each other. It concentrates on the life and writing of Olive Garnett and Sergei Stepniak, as they are focal points of the contacts between English people and Russians in London in the 1890s. The figures of Garnett and Stepniak are set against the background of Russian revolutionary activity in Britain at that period. The findings described in this article raise questions about Anglo-Russian relations and their potential significance in the years preceding the October Revolution.
Epidural Analgesia During Labor and Delivery: Effects on the Initiation and Continuation of Effective Breastfeeding
Authors: Chang Zorina Marzan , Heaman Maureen I.
Published: August 2005

This prospective cohort study examined the association between epidural analgesia during labor and delivery, infant neurobehavioral status, and the initiation and continuation of effective breastfeeding. Healthy, term infants delivered vaginally by mothers who received epidural analgesia (n = 52) or no analgesia (n = 63) during labor and delivery were assessed at 8 to 12 hours postpartum, followed by a telephone interview with the mothers at 4 weeks postpartum. There was no significant difference between the epidural analgesia and no-analgesia groups in breastfeeding effectiveness or infant neurobehavioral status at 8 to 12 hours or in the proportion of mothers continuing to breastfeed at 4 weeks. Therefore, epidural analgesia did not appear to inhibit effective breastfeeding. There was a positive correlation between infant neurobehavioral status and breastfeeding effectiveness (Spearman [.rho] = 0.48, P = .01), suggesting that neurobehavioral assessment may prove beneficial in identifying infants at greater risk for breastfeeding difficulties.
Exclusive Breastfeeding in 3 Rural Localities in Mexico
Authors: Flores Mario , Pasquel Marta Rivera , Maulén Irene , Rivera Juan
Published: August 2005

The purpose of this study was to assess the factors associated with exclusive breastfeeding (EBF) during the first 6 months of life. A prospective, cohort study was conducted in 291 newborn children in 3 semirural localities in Mexico. Data were collected on infant-feeding practices, anthropometry, morbidity, and maternal and household characteristics. Two-stage multivariate regression models were used for statistical analysis. Prevalence of EBF was 50% at day 5. Average duration of EBF was 2.18 months. According to the 2-stage model, maternal age, maternal work, and better socioeconomic conditions were associated with EBF at day 5. Infant nutritional status, prevalence of diarrhea, giving colostrum to the newborn, and maternal experience in breastfeeding were associated with duration of EBF. The prevalence of EBF and its duration were much shorter than recommended internationally. EBF during the early days of life and EBF duration are 2 different processes that are determined by different factors.
A Review of Toward a Pneumatological Theology: Pentecostal and Ecumenical Perspectives on Ecclesiology Soteriology and Theology of Mission by Veli-Matti Kärkkäinen
Authors: Clarke Clifton
Published: August 2005

Toward a Pneumatological Theology by Veli-Matti Kärkkäinen is an insightful investigation into the possibility of a truly ecumenical and conciliar pneumatic theology. Kärkkäinen develops his reflection on a pneumatological theology in critical dialogue with Pentecostal and Catholic traditions, drawing upon and expanding the theological insights that have emanated from the various Quinqueniums of the Catholic-Pentecostal dialogue. This review applauds Kärkkäinen’s effort of bringing together historical and theological traditions as far apart as Pentecostal and Catholic in search of a greater ecumenical understanding of God the Holy Spirit. The review, however, warns of the dangers of oversimplification and false dichotomizing, when considering such complex and pluriform traditions.
Adrenocorticotropic Hormone-Mediated Signaling Cascades Coordinate a Cyclic Pattern of Steroidogenic Factor 1-Dependent Transcriptional Activation
Authors: Winnay Jonathon N. , Hammer Gary D.
Published: August 2005

Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that has emerged as a critical mediator of endocrine function at multiple levels of the hypothalamic-pituitary-steroidogenic axis. Within the adrenal cortex, ACTH-dependent transcriptional responses, including transcriptional activation of several key steroidogenic enzymes within the steroid biosynthetic pathway, are largely dependent upon SF-1 action. The absence of a bona fide endogenous eukaryotic ligand for SF-1 suggests that signaling pathway activation downstream of the melanocortin 2 receptor (Mc2r) modulates this transcriptional response. We have used the chromatin immunoprecipitation assay to examine the temporal formation of ACTH-dependent transcription complexes on the Mc2r gene promoter. In parallel, ACTH-dependent signaling events were examined in an attempt to correlate transcriptional events with the upstream activation of signaling pathways. Our results demonstrate that ACTH-dependent signaling cascades modulate the temporal dynamics of SF-1-dependent complex assembly on the Mc2r promoter. Strikingly, the pattern of SF-1 recruitment and the subsequent attainment of active rounds of transcription support a kinetic model of SF-1 transcriptional activation, a model originally established in the context of ligand-dependent transcription by several classical nuclear hormone receptors. An assessment of the major ACTH-dependent signaling pathways highlights pivotal roles for the MAPK as well as the cAMP-dependent protein kinase A pathway in the entrainment of SF-1-mediated transcriptional events. In addition, the current study demonstrates that specific enzymatic activities are capable of regulating distinct facets of a highly ordered transcriptional response.
Detection of brain injury by fatty acid-binding proteins
Authors: Pelsers Maurice M. A. L. , Glatz Jan F. C.
Published: August 2005

The rapid detection of brain injury (neuronal damage in general) is an important parameter in the management of cerebrovascular accidents, especially in hemorrhagic and/or ischemic events. Two types of 15-kDa cytoplasmic fatty acid-binding proteins (FABPs), brain-type FABP and heart-type FABP, have recently been postulated as novel markers for brain injury detection. Here we review the possible roles of these FABPs as rapid diagnostic markers for the detection of brain injury due to cerebrovascular accident, trauma or neurodegenerative diseases. The occurrence of brain- and heart-type FABPs in segments of the human brain is also described. Although only limited amounts of data are available, brain- and heart-type FABPs show higher sensitivities and specificities than protein S100 and neuron specific enolase in the rapid detection of brain injury in stroke, trauma and neurodegenerative diseases.
The NFκB pathway and endocrine-resistant breast cancer
Authors: Zhou Y , Eppenberger-Castori S , Eppenberger U , Benz C C
Published: August 2005

Endocrine therapy with an estrogen receptor (ER)-targeted antiestrogen, such as tamoxifen, or estrogen ablation by aromatase inhibitors is clinically indicated for the management of all forms of ER-positive breast cancer. However, 30–50% of ER-positive breast cancer cases fail to benefit clinically from endocrine therapy alone, and recent molecular evidence suggests that ‘crosstalk’ pathways originating from activated receptor tyrosine kinases and/or other proliferative and survival signals may be contributing to this endocrine resistance. Molecular identification and validation of candidate ER crosstalking pathways will likely lead to clinically important prognostic markers and targets for the application of novel therapeutics in combination with standard endocrine agents. This review focuses on a critical survival and proliferation pathway involving activation of nuclear factor-κB (NFκB), a family of ubiquitously expressed transcription factors that for nearly two decades have been known to be critical regulators of mammalian immune and inflammatory responses, and more recently have been associated with chemotherapy resistance. With the demonstration that activation of NFκB is absolutely required for normal mammary gland development, NFκB involvment in human breast cancers was initially explored and linked to the development of hormone-independent (ER-negative) breast cancer. Newer clinical evidence now implicates NFκB activation, particularly DNA-binding by the p50 subunit of NFκB, as a potential prognostic marker capable of identifying a high-risk subset of ER-positive, primary breast cancers destined for early relapse despite adjuvant endocrine therapy with tamoxifen. Furthermore, initial preclinical studies suggest that treatment strategies designed to prevent or interrupt activation of NFκB in cell-line models of these more aggressive, ER-positive breast cancers can restore their sensitivity to such standard endocrine agents as tamoxifen.
Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer
Authors: Gee J M , Robertson J F , Gutteridge E , Ellis I O , Pinder S E , Rubini M , Nicholson R I
Published: August 2005

Breast cancer models of acquired tamoxifen resistance, oestrogen receptor (ER)+ /ER− de novo resistance and gene transfer studies cumulatively demonstrate the increased importance of growth factor receptor signalling, notably the epidermal growth factor receptor (EGFR)/HER2, in tamoxifen resistance. Our recent in vitro studies also suggest that EGFR signalling productively cross-talks with insulin-like growth factor receptor (IGF-1R) and, where present, activates ER on key AF-1 serine residues to facilitate acquired tamoxifen-resistant growth. This paper presents our immunohistochemical evidence that EGFR/HER2 signalling (i.e. transforming growth factor (TGF)α, EGFR and HER2 expression; phosphorylation of EGFR, HER2 and ERK1/2 MAP kinase) is also prominent in clinical de novo resistant and modestly increased in acquired tamoxifen-resistant states, suggesting that anti-EGFR/HER2 strategies may prove valuable treatments. Primary breast cancer samples employed were obtained for (1) patients subsequently treated with tamoxifen for advanced disease where endocrine response and survival data were available and (2) ER+ elderly patients during tamoxifen response and relapse. We also present our clinical immunohistochemical findings that IGF-1R expression, its phosphorylation on tyrosine 1316, and also phosphorylation on serine 118 of ER are not only prominent in ER+ tamoxifen-responsive disease, but are also detectable in ER+ de novo and acquired tamoxifen-resistant breast cancer, where there is evidence of EGFR/ER cross-talk. Our data suggest that agents to deplete effectively ER or IGF-1R signalling may be of value in treating ER+ de novo/acquired tamoxifen resistance in addition to tamoxifen-responsive disease in vivo. IGF-1R inhibitors may also prove valuable in ER− patients, since considerable IGF-1R signalling activity was apparent within ~50% of such tumours.
Acquired resistance to oestrogen deprivation: role for growth factor signalling kinases/oestrogen receptor cross-talk revealed in new MCF-7X model
Authors: Staka Cindy M , Nicholson Robert I , Gee Julia M W
Published: August 2005

In vitro models of long-term oestrogen deprivation utilise increased oestrogen receptor (ER) and are oestrogen hypersensitive, with emerging evidence that growth factor signalling contributes and interacts with ER. However, such models are commonly derived in the presence of serum growth factors that may force the resistance mechanism. Our new in vitro model, MCF-7X, has thus been developed under conditions of both oestrogen and growth factor depletion. ER expression, serine 118 phosphorylation on this receptor and its transcriptional activity were modestly increased compared to the parental MCF-7 cells, although MCF-7X cells were not oestrogen hypersensitive. Faslodex (0.1 μM) partially decreased ER and its transcriptional activity, with associated decreases in serine 118 phosphorylation. Faslodex inhibited MCF-7X growth by 50% for 10 weeks. Classical growth factor receptors did not impact on MCF-7X growth and only a modest contribution for MAP kinase was revealed using PD98059 (25 μM; 35% inhibition for 3 weeks). However, the phosphatidylinositol-3-OH (PI3)-kinase inhibitor LY294002 (5 μM) inhibited MCF-7X growth by 65% for 10 weeks. In contrast to PD98059, LY294002 also partially-inhibited ER transcriptional activity and decreased serine 167 ER phosphorylation. Co-treatment with faslodex plus LY294002 to decrease activity of both serine 118 and 167 proved superior vs the single agents in decreasing ER transcriptional activity and MCF-7X growth (90% inhibition for 25 weeks). However, triple treatment including PD98059 was required to prevent resistance in MCF-7X, an event dependent on maximal depletion of serine 118 phosphorylation and ER transcriptional activity. Kinases clearly contribute in resistance to oestrogen deprivation, cross-talking with ER signalling via AF-1 phosphorylation. While inhibiting each pathway has potential to treat this state, combined therapy targeting all regulators of ER phosphorylation may be required to block subsequent emergence of resistance.
Long-term estradiol deprivation in breast cancer cells up-regulates growth factor signaling and enhances estrogen sensitivity
Authors: Santen R J , Song R X , Zhang Z , Kumar R , Jeng M-H , Masamura A , Lawrence J , Berstein L , Yue W
Published: August 2005

Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regression. We have utilized in vitro and in vivo model systems to examine the biologic processes whereby long-term estradiol deprivation (LTED) causes cells to adapt and develop hypersensitivity to estradiol. Several mechanisms are associated with this response, including up-regulation of estrogen receptor-α (ERα) and the MAP kinase, phosphoinositol 3 kinase (PI3-K) and mammalian target of rapamycin (mTOR) growth factor pathways. ERα is four- to tenfold up-regulated and co-opts a classical growth factor pathway using Shc, Grb-2 and Sos. This induces rapid non-genomic effects which are enhanced in LTED cells. The molecules involved in the non-genomic signaling process have been identified. Estradiol binds to cell membrane-associated ERα, which physically associates with the adaptor protein Shc, and induces its phosphorylation. In turn, Shc binds Grb-2 and Sos, which result in the rapid activation of MAP kinase. These non-genomic effects of estradiol produce biologic effects as evidenced by Elk-1 activation and by morphologic changes in cell membranes. Additional effects include activation of the PI3-K and mTOR pathways through estradiol-induced binding of ERα to the IGF-I and epidermal growth factor receptors. A major question is how ERα locates in the plasma membrane since it does not contain an inherent membrane localization signal. We have provided evidence that the IGF-I receptor serves as an anchor for ERα in the plasma membrane. Estradiol causes phosphorylation of the adaptor protein, Shc and the IGF-I receptor itself. Shc, after binding to ERα, serves as the ‘bus’ which carries ERα to Shc-binding sites on the activated IGF-I receptors. Use of small inhibitor (si) RNA methodology to knockdown Shc allows the conclusion that Shc is needed for ERα to localize in the plasma membrane. In order to abrogate growth factor-induced hypersensitivity, we have utilized a drug, farnesylthiosalicylic acid, which blocks the binding of GTP-Ras to its membrane acceptor protein, galectin 1, and reduces the activation of MAP kinase. We have also shown that this drug is a potent inhibitor of mTOR as an additional mechanism of inhibition of cell proliferation. The concept of ‘adaptive hypersensitivity’ and the mechanisms responsible for this phenomenon have important clinical implications. The efficacy of aromatase inhibitors in patients relapsing on tamoxifen could be explained by this mechanism and inhibitors of growth factor pathways should reverse the hypersensitivity phenomenon and result in prolongation of the efficacy of hormonal therapy for breast cancer.
Elevated ERK1/ERK2/estrogen receptor cross-talk enhances estrogen-mediated signaling during long-term estrogen deprivation
Authors: Martin Lesley-Ann , Farmer Ian , Johnston Stephen R D , Ali Simak , Dowsett Mitch
Published: August 2005

The knowledge that steroids play a pivotal role in the development of breast cancer has been exploited clinically by the development of endocrine treatments. These have sought to perturb the steroid hormone environment of the tumour cells, predominately by withdrawal or antagonism of oestrogen. Unfortunately, the beneficial actions of existing endocrine treatments are attenuated by the ability of tumours to circumvent the need for steroid hormones, whilst in most cases, retaining the nuclear steroid receptors. The mechanisms involved in resistance to estrogen deprivation are of major clinical relevance for optimal treatment of breast cancer patients and the development of new therapeutic regimes. We have shown that long-term culture of MCF7 cells in medium depleted of oestrogen (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of both ERα phosphorylated on Ser118 and ERK1/ERK2. Our data suggest elevated ERK1/ERK2 activity results wholly or in part from enhanced ERBB2 expression in the LTED cells. These cells showed greater sensitivity to the tyrosine kinase inhibitor ZD1839 in both ERα-mediated transcription and growth assays compared with the wt-MCF7. Similarly the MEK inhibitor U0126 decreased basal ERα-mediated transcription and proliferation in the LTED cells by 50% and reduced their sensitivity to the proliferative effects of E2 10-fold, whilst having no effect on the wild type (wt). However, complete suppression of ERK1/ERK2 activity in the LTED cells did not inhibit ERα Ser118 phosphorylation suggesting that the cells remained ligand-dependent. This was further confirmed by the increased sensitivity of the LTED cells to the growth suppressive effects of ICI 182,780 and suggested that the LTED cells remained wholly or partially dependent on oestrogen receptor (ER)/oestrogen responsive elements directed growth. These findings suggest that treatments targeted at growth factor signalling pathways may be useful in patients acquiring resistance to oestrogen deprivation with aromatase inhibitors and that the pure anti-oestrogen ICI 182,780 may also be effective by blocking or destabilizing ER and hence disrupting cross-talk.
Detection of an unexpected subtelomeric 15q26.2 → qter deletion in a little girl: Clinical and cytogenetic studies
Authors: Pinson L. , Perrin A. , Plouzennec C. , Parent P. , Metz C. , Collet M. , Le Bris M.J. , Douet‐Guilbert N. , Morel F. , De Braekeleer M.
Published: August 2005

Unlike the small proximal 15q deletions causing Prader‐Willi and/or Angelman syndrome, distal deletions of the terminal long arm of chromosome 15 have rarely been described. To the best of our knowledge, only four patients with a pure terminal 15q deletion have been documented in the literature. We report here on an unexpected abnormal hybridization pattern for the 15q specific subtelomeric control probe (clone 154P1) of the commercial SNRPN probe in a girl referred for suspicion of Angelman syndrome. Investigation by fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones defined a partial monosomy 15q26.2 → 15qter for a minimal critical region of approximately 5.7 Mb, which is the most distal de novo 15qter deletion reported to date. All the de novo 15qter deletion cases, including ours, presented with pre‐ and post‐natal growth retardation related to the loss of one copy of the IGF1R gene. Based on the comparaison with the previous published cases and owing to the clinical phenotype of our patient, we define a new subtelomeric 15qter syndrome which would be characterized by intrauterine growth retardation and global post‐natal growth failure, variable mental retardation, facial anomalies including relative micrognathia and triangular facies and minor malformations of the extremities including proximally placed thumbs, cubitus valgus, and brachydactyly with tappering of the digits. © 2005 Wiley‐Liss, Inc.
Sexual dimorphism in metapodial and phalanges length ratios in the wood mouse
Authors: Leoni Barbara , Canova Luca , Saino Nicola
Published: August 2005

Relative length of metapodials and digits is sexually dimorphic in most primates and one rodent and one bird species studied so far. Recently, interest in digit ratios has increased because of their correlation with diverse physiological, psychological, and performance traits in humans. These correlations may reflect the effect of androgens during early ontogeny on digit development and their long‐term organizational effects on extragenital organs. Inter‐ and intrasexual variation in digit ratios may be ultimately controlled by modulation of the expression of Hoxa and Hoxd genes. Since Hox genes are conserved in vertebrates, similar patterns of sex‐related variation in length ratios may be expected across taxa. In fact, sexual dimorphism in length ratios has been documented for metapodials or digit bones in nonhuman vertebrates, but the specific pattern of sex‐related variation varies considerably. However, no study has investigated sexual dimorphism in length ratios between all ray segments (metapodials plus phalanges) using osteometrical measures. In an outbred wild population of wood mice (Apodemus sylvaticus), we found extensive sex‐related variation in ratios between osteometrical length of the phalanges, but not metatarsals, similar to that recorded on undissected digits of humans and laboratory mice. Most sexually dimorphic ratios involved the second digit. We found very weak evidence for directional asymmetry in length ratios. The present study shows that sex‐related variation in length ratios between digit segments observed in mammals may actually depend on relative bone length. Hence, other species may be used to investigate the causal and semeiotic implications of variation in human digit ratios. © 2005 Wiley‐Liss, Inc.
Identification of chromosome arm 9p as the most frequent target of homozygous deletions in lung cancer
Authors: Sato Masamitsu , Takahashi Kenji , Nagayama Kazuhiro , Arai Yasuhito , Ito Nobue , Okada Mitsumasa , Minna John D. , Yokota Jun , Kohno Takashi
Published: August 2005

Genome scanning at a 1‐Mb resolution was undertaken in 29 lung cancer cell lines to clarify the distribution of homozygous (i.e., both allele) deletions along lung cancer genomes, using a high‐resolution single nucleotide polymorphism array. Eighteen regions, including two known tumor suppressor loci, CDKN2A at 9p21 and FHIT at 3p14, were found homozygously deleted. Frequencies of deletions at the 18 regions were evaluated by genomic polymerase chain reaction in 78 lung cancer cell lines. Seven regions, 2q24, 3p14, 5q11, 9p21, 9p23, 11q14, and 21q21, were homozygously deleted in two or more cell lines. The CDKN2A locus at 9p21 was most frequently deleted (20/78, 26%), and the deletions were detected exclusively in non‐small‐cell lung carcinomas (NSCLCs). The PTPRD (protein tyrosine phosphatase receptor type D) locus at 9p23 was the second‐most frequently deleted (8/78, 10%), and the deletions were detected in both small‐cell lung carcinomas (SCLC) and NSCLC. In addition, the 9p24 region was deleted in a NSCLC. In total, 24 (31%) cell lines carried at least one deletion on chromosome arm 9p, while deletions on the remaining chromosome arms were observed at most in four (5%) cell lines. Deletions at 9p24, 9p23, and 9p21 were not contiguous with one another, and preferential co‐occurrence or mutual exclusiveness for the deletions at these three loci was not observed. Thus, it was indicated that 9p is the most frequent target of homozygous deletions in lung cancer, suggesting that the arm contains multiple lung tumor suppressor genes and/or genomic features fragile during lung carcinogenesis. © 2005 Wiley‐Liss, Inc.
Back Cover: Macromol. Biosci. 8/2005
Authors: Barsberg Søren , Matousek Pavel , Towrie Mike
Published: August 2005

Back Cover: The combination of Kerr gated Raman spectroscopy and the structural selectivity of a probing treatment, e.g., laccase‐ABTS, enables selective analysis of structural motifs in lignin. The laser photon energy and probing method determine the selectivity via the Resonance Raman effect and the reactivity of lignin motifs, respectively. Further details can be found in the Full Paper by S. Barsberg,* P. Matousek, and M. Towrie on page 743.
Cover Picture: Macromol. Mater. Eng. 8/2005
Authors: Ray Suprakas Sinha , Bousmina Mosto , Okamoto Kazuaki
Published: August 2005

Cover: The picture on the cover shows the structure and dynamic mechanical properties of neat poly(butylene succinate‐co‐adipate) and its nanocomposites with organically modified montmorillonite. Further can be found in the article by S. Sinha Ray, M. Bousmina,* and K. Okamoto on page 759.
Cover Picture: Macromol. Theory Simul. 7/2005
Authors: Martínez‐Haya Bruno , Gordillo M. C.
Published: August 2005

Cover: The conformational behavior of flexible chain polymers confined in narrow pores has been studied by computer simulations. It is shown that the crowding of the system with spherical depleting agents opposes the effective stretching forces imposed by confinement, and may be employed to tune the folding of the polymer and the conformational scaling laws. Further details can be found in the Full Paper by B. Martínez‐Haya* and M. C. Gordillo on page 421.
Solvent effects in the polymerization of propylene catalyzed by octahedral complexes
Authors: Volkis Victoria , Smolensky Elena , Lisovskii Anatoli , Eisen Moris S.
Published: August 2005

The effect of solvents (toluene, dichloromethane, and hexane) was studied on the polymerization of propylene with the octahedral complexes bis(trimethylsilyl)benzamidinate titanium dichloride(a), bis(acetylacetonate) titanium dichloride(b), and bis(diethylamino) titanium di‐2‐(diphenylphosphanylamino)pyridine as catalytic precursors and methylalumoxane as the cocatalyst. For comparison, the polymerization was also performed in plain liquid propylene without the addition of any solvent. The obtained polymers were fractionated by refluxing hexane. The activity of the complexes and the molecular weights and tacticities of the whole polymers and their different fractions were the studied parameters. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4505–4516, 2005
Polyglutamine homopolymers having 8–45 residues form slablike β‐crystallite assemblies
Authors: Sharma Deepak , Shinchuk Leonid M. , Inouye Hideyo , Wetzel Ronald , Kirschner Daniel A.
Published: August 2005

At least nine inherited neurodegenerative diseases, including Huntington's, are caused by poly(L‐glutamine) (polyGln, polyQ) expansions > 35–40 repeats in widely or ubiquitously expressed proteins. Except for their expansions, these proteins have no sequence homologies, and their functions mostly remain unknown. Although each disease is characterized by a distinct pathology specific to a subset of neuronal cells, the formation of neuronal intranuclear aggregates containing protein with an expanded polyQ is the hallmark and common feature to most polyQ disorders. The neurodegeneration is thought to be caused by a toxic gain of function that occurs at the protein level and depends on the length of the expansion: Longer repeats cause earlier age of onset and more severe symptoms. To address whether there is a structural difference between polyQ having < 40 versus > 40 residues, we undertook an X‐ray fiber diffraction study of synthetic polyQ peptides having varying numbers of residues: Ac‐Q8‐NH2, D2Q15K2, K2Q28K2, and K2Q45K2. These particular lengths bracket both the range of normalcy (9–36 repeats) and the pathological (45 repeats), and therefore could be indicative of the structural changes expected in expanded polyQ domains. Contrary to expectations of different length‐dependent morphologies, we accounted for all the X‐ray patterns by slablike, β‐sheet structures, ∼20 Å thick in the β‐chain direction, all having similar monoclinic lattices. Moreover, the slab thickness indicates that K2Q45K2, rather than forming a water‐filled nanotube, must form multiple reverse turns. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Lyapunov functions for positive linear evolution problems
Authors: Stephan H.
Published: August 2005

We rigorously investigate the time monotonicity of Lyapunov functions for general positive linear evolution problems, including degenerate problems. This can be done by considering the problem in the convex set of probability measures and finding a general inequality for such Radon measures and Markov operators. For linear evolution problems (with discrete or continuous time), the existence of time monotone Lyapunov functions is not a consequence of any physical properties, but of the positivity and norm conservation of the equation. In some special cases the structure of such equations is given. Moreover, we describe completely the case of time constant Lyapunov functions – a property of deterministic dynamical systems.
Stationary energy models for semiconductor devices with incompletely ionized impurities
Authors: Glitzky A. , Hünlich R.
Published: August 2005

Dedicated to Professor Herbert Gajewski on his 65th birthday

The paper deals with two‐dimensional stationary energy models for semiconductor devices, which contain incompletely ionized impurities. We reduce the problem to a strongly coupled nonlinear system of four equations, which is elliptic in nondegenerated states. Heterostructures as well as mixed boundary conditions have to be taken into account. For boundary data which are compatible with thermodynamic equilibrium there exists a thermodynamic equilibrium. Using regularity results for systems of strongly coupled linear elliptic differential equations with mixed boundary conditions and nonsmooth data and applying the Implicit Function Theorem we prove that in a suitable neighbourhood of such a thermodynamic equilibrium there exists a unique stationary solution, too.
Discrete transparent boundary conditions for transient kp‐Schrödinger equations with application to quantum heterostructures
Authors: Zisowsky A. , Arnold A. , Ehrhardt M. , Koprucki Th.
Published: August 2005

This work is concerned with transparent boundary conditions (TBCs) for systems of Schrödinger‐type equations, namely the time‐dependent kp‐Schrödinger equations. These TBCs are constructed for the fully discrete scheme (Crank‐Nicolson, finite differences), in order to maintain unconditional stability of the scheme and to avoid numerical reflections. The discrete transparent boundary conditions (DTBCs) are discrete convolutions in time and are constructed using the 𝒵‐transformed solution of the exterior problem. We will analyse the numerical error of these convolution coefficients caused by the inverse 𝒵‐transformation. Since the DTBCs are non‐local in time and thus very costly to evaluate, we present approximate DTBCs of a sum‐of‐exponentials form that allow for a fast calculation of the boundary terms.