scispace - formally typeset
Search or ask a question

Showing papers by "University of Basel published in 2003"


Journal ArticleDOI
TL;DR: The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.
Abstract: SWISS-MODEL (http://swissmodel.expasy.org) is a server for automated comparative modeling of three-dimensional (3D) protein structures. It pioneered the field of automated modeling starting in 1993 and is the most widely-used free web-based automated modeling facility today. In 2002 the server computed 120 000 user requests for 3D protein models. SWISS-MODEL provides several levels of user interaction through its World Wide Web interface: in the 'first approach mode' only an amino acid sequence of a protein is submitted to build a 3D model. Template selection, alignment and model building are done completely automated by the server. In the 'alignment mode', the modeling process is based on a user-defined target-template alignment. Complex modeling tasks can be handled with the 'project mode' using DeepView (Swiss-PdbViewer), an integrated sequence-to-structure workbench. All models are sent back via email with a detailed modeling report. WhatCheck analyses and ANOLEA evaluations are provided optionally. The reliability of SWISS-MODEL is continuously evaluated in the EVA-CM project. The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.

5,208 citations


Journal ArticleDOI
TL;DR: In this paper, a comprehensive report entitled Adherence to Long-Term Therapies: Evidence for Action w1x was published, focusing on nine chronic conditions and their risk factors.
Abstract: The World Health Organization(WHO) has recently published a comprehensive report entitled Adherence to Long-Term Therapies: Evidence for Action w1x. This report focuses on nine chronic conditions and their riskfactors. The conditions reviewed are hypertension, tobacco smoking cessation, asthma, cancer (palliative care), depression, diabetes, epilepsy, HIV yAIDS and tuberculosis. The report reviewed the available literature on the epidemiology of nonadherence worldwide; it stressed the multi-factorial nature of nonadherence, it identified health systems and health care teams as significant determinants to good adherence and discussed the health and economic consequences of nonadherence as well as some strategies for improving it. This report has major relevance for cardiovascular nurses. Cardiovascular disease is and will remain a major challenge for health care professionals and health care systems, and it contributes significantly to the global burden of disease in both developed and developing countriesw2x. Nonadherence to treatment recommendations in patients with cardiovascular risk-factors as well as patients with cardiovascular disease is widespread, and it is a major factor contributing to poor outcome. Nurses are excellently positioned to target the behavioral dimension of chronic disease management. They can improve outcomes by developing and implementing adherence-enhancing strategies to reduce cardiovascular risk-factors, and to enhance adherence with non-smoking, diet, exercise and medication regimens w3x. The value of this WHO report is not only that it comprehensively reviews the current state of the literature including hypertension and tobacco smoking cessation, but also it highlights the need for a multi-disciplinary approach to adherence, emphasizes system factors that need to be addressed in successfully implementing adherence-enhancing strategies. Moreover, it also provides illustrative examples of the ways in which professionals have contributed in their own fields of expertise including cardiovascular care among other fields. This report, therefore, provides an instrument to cardiovascular nurses to expand the behavioral dimension of their patient management strategies, to teach students at undergraduate and graduate level, to guide their research endeavors, to guide policy makers, ultimately with the goal to improve outcomes of populations.

4,049 citations


Journal ArticleDOI
TL;DR: Imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML and was better tolerated than combination therapy.
Abstract: Background Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. Methods We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. Results After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 perce...

3,399 citations


Journal ArticleDOI
TL;DR: This paper presents a method for face recognition across variations in pose, ranging from frontal to profile views, and across a wide range of illuminations, including cast shadows and specular reflections, using computer graphics.
Abstract: This paper presents a method for face recognition across variations in pose, ranging from frontal to profile views, and across a wide range of illuminations, including cast shadows and specular reflections. To account for these variations, the algorithm simulates the process of image formation in 3D space, using computer graphics, and it estimates 3D shape and texture of faces from single images. The estimate is achieved by fitting a statistical, morphable model of 3D faces to images. The model is learned from a set of textured 3D scans of heads. We describe the construction of the morphable model, an algorithm to fit the model to images, and a framework for face identification. In this framework, faces are represented by model parameters for 3D shape and texture. We present results obtained with 4,488 images from the publicly available CMU-PIE database and 1,940 images from the FERET database.

2,187 citations


Journal ArticleDOI
TL;DR: It is shown that there is a profound sexual dimorphism of Acrp30 levels and complex distribution in serum and a new model for in vivo activation of the protein, implicating a serum reductase activity is suggested.

1,083 citations


Journal ArticleDOI
TL;DR: This article presents international consensus criteria for and classification of AbAR developed based on discussions held at the Sixth Banff Conference on Allograft Pathology in 2001, to be revisited as additional data accumulate in this important area of renal transplantation.

1,018 citations


Journal ArticleDOI
TL;DR: A single intervention with vitamin D plus calcium over a 3‐month period reduced the risk of falling by 49% compared with calcium alone, andMusculoskeletal function improved significantly in the Cal+D‐group (p = 0.0094).
Abstract: Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed upg p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

955 citations


Journal ArticleDOI
TL;DR: In this article, the authors explore current levels of nonstructural carbon in trees in natural forests in order to estimate the potential for a carbon-driven stimulation of growth, and conclude that, irrespective of the reason for its periodic cessation, growth does not seem to be limited by carbon supply.
Abstract: 1 The ongoing enrichment of the atmosphere with CO2 raises the question of whether growth of forest trees, which represent close to 90 global biomass carbon, is still carbon limited at current concentrations of close to 370 p.p.m. As photosynthesis of C3 plants is not CO2 -saturated at such concentrations, enhanced `source activity` of leaves could stimulate `sink activity` (i.e. growth) of plants, provided other resources and developmental controls permit. I explore current levels of non-structural carbon in trees in natural forests in order to estimate the potential for a carbon-driven stimulation of growth. 2 The concentration of non-structural carbohydrates (NSC) in tree tissues is considered a measure of carbon shortage or surplus for growth. A periodic reduction of NSC pools indicates either that carbon demand exceeds con-current supply, or that both source and sink activity are low. A steady, very high NSC concentration is likely to indicate that photosynthesis fully meets, or even exeeds, that needed for growth (surplus assimilates accumulate). 3 The analysis presented here considers data for mature trees in four climatic zones: the high elevation treeline (in Mexico, the Alps and Northern Sweden), a temperate lowland forest of central Europe, Mediterranean sclerophyllous woodland and a semideciduous tropical forest in Panama. 4 In all four climatic regions, periods of reduced or zero growth show maximum C-loading of trees (source activity exceeding demand), except for dry midsummer in the Mediterranean. NSC pools are generally high throughout the year, and are not significantly affected by mass fruiting episodes. 5 It is concluded that, irrespective of the reason for its periodic cessation, growth does not seem to be limited by carbon supply. Instead, in all the cases examined, sink activity and its direct control by the environment or developmental constraints, restricts biomass production of trees under current ambient CO2 concentrations. 6 The current carbohydrate charging of mature wild trees from the tropics to the cold limit of tree growth suggests that little (if any) leeway exists for further CO2-fertilization effects on growth.

930 citations


Journal ArticleDOI
18 Sep 2003-Nature
TL;DR: It is shown that the von Hippel–Lindau tumour suppressor protein pVHL negatively regulates CX CR4 expression owing to its capacity to target hypoxia-inducible factor (HIF) for degradation under normoxic conditions, resulting in HIF-dependent CXCR4 activation.
Abstract: Organ-specific metastasis is governed, in part, by interactions between chemokine receptors on cancer cells and matching chemokines in target organs. For example, malignant breast cancer cells express the chemokine receptor CXCR4 and commonly metastasize to organs that are an abundant source of the CXCR4-specific ligand stromal cell-derived factor-1α (ref. 1). It is still uncertain how an evolving tumour cell is reprogrammed to express CXCR4, thus implementing the tendency to metastasize to specific organs. Here we show that the von Hippel–Lindau tumour suppressor protein pVHL negatively regulates CXCR4 expression owing to its capacity to target hypoxia-inducible factor (HIF) for degradation under normoxic conditions. This process is suppressed under hypoxic conditions, resulting in HIF-dependent CXCR4 activation. An analysis of clear cell renal carcinoma that manifests mutation of the VHL gene in most cases revealed an association of strong CXCR4 expression with poor tumour-specific survival. These results suggest a mechanism for CXCR4 activation during tumour cell evolution and imply that VHL inactivation acquired by incipient tumour cells early in tumorigenesis confers not only a selective survival advantage but also the tendency to home to selected organs.

906 citations


Journal ArticleDOI
TL;DR: In this paper, the authors identify metabolites of the mevalonate pathway as the tumor ligands that activate TCR-γδ cells, and demonstrate that when metabolite accumulation is induced by overexpressing HMGR or by treatment with nitrogen-containing bisphosphonate drugs, tumor cells derived from many tissues acquire the capacity to stimulate the same T cell receptor (TCR-γα)-γα population.
Abstract: T lymphocytes expressing the T cell receptor (TCR)-γδ recognize unknown antigens on tumor cells. Here we identify metabolites of the mevalonate pathway as the tumor ligands that activate TCR-γδ cells. In tumor cells, blockade of hydroxy-methylglutaryl-CoA reductase (HMGR), the rate limiting enzyme of the mevalonate pathway, prevents both accumulation of mevalonate metabolites and recognition by TCR-γδ cells. When metabolite accumulation is induced by overexpressing HMGR or by treatment with nitrogen-containing bisphosphonate drugs, tumor cells derived from many tissues acquire the capacity to stimulate the same TCR-γδ population. Accumulation of mevalonate metabolites in tumor cells is a powerful danger signal that activates the immune response and may represent a novel target of tumor immunotherapy.

769 citations


Journal ArticleDOI
TL;DR: It is reported that placental growth factor (PGF) regulates inter- and intramolecular cross talk between the VEGF RTKs Flt1 and Flk1, which is likely to have therapeutic implications, as treatment with VegF/PGF heterodimer or a combination of VEGf plus PGF increased ischemic myocardial angiogenesis in a mouse model that was refractory to V EGF alone.
Abstract: Therapeutic angiogenesis is likely to require the administration of factors that complement each other. Activation of the receptor tyrosine kinase (RTK) Flk1 by vascular endothelial growth factor (VEGF) is crucial, but molecular interactions of other factors with VEGF and Flk1 have been studied to a limited extent. Here we report that placental growth factor (PGF, also known as PlGF) regulates inter- and intramolecular cross talk between the VEGF RTKs Flt1 and Flk1. Activation of Flt1 by PGF resulted in intermolecular transphosphorylation of Flk1, thereby amplifying VEGF-driven angiogenesis through Flk1. Even though VEGF and PGF both bind Flt1, PGF uniquely stimulated the phosphorylation of specific Flt1 tyrosine residues and the expression of distinct downstream target genes. Furthermore, the VEGF/PGF heterodimer activated intramolecular VEGF receptor cross talk through formation of Flk1/Flt1 heterodimers. The inter- and intramolecular VEGF receptor cross talk is likely to have therapeutic implications, as treatment with VEGF/PGF heterodimer or a combination of VEGF plus PGF increased ischemic myocardial angiogenesis in a mouse model that was refractory to VEGF alone.

Journal ArticleDOI
09 Jan 2003-Nature
TL;DR: In this article, the authors used infrared-laser atomic-force microscopy to reveal the native arrangement of rhodopsin, which forms paracrystalline arrays of dimers in mouse disc membranes.
Abstract: Neat rows of paired photon receptors are caught on camera in their natural state. In vertebrate retinal photoreceptors, the rod outer-segment disc membranes contain densely packed rhodopsin molecules for optimal light absorption and subsequent amplification by the visual signalling cascade1, but how these photon receptors are organized with respect to each other is not known. Here we use infrared-laser atomic-force microscopy to reveal the native arrangement of rhodopsin, which forms paracrystalline arrays of dimers in mouse disc membranes. The visualization of these closely packed rhodopsin dimers in native membranes gives experimental support to earlier inferences about their supramolecular structure2,3 and provides insight into how light signalling is controlled.

Journal ArticleDOI
TL;DR: The increased land use intensity was correlated with a decrease in AMF species richness and with a preferential selection of species that colonized roots slowly but formed spores rapidly.
Abstract: The impact of land use intensity on the diversity of arbuscular mycorrhizal fungi (AMF) was investigated at eight sites in the “three-country corner” of France, Germany, and Switzerland. Three sites were low-input, species-rich grasslands. Two sites represented low- to moderate-input farming with a 7-year crop rotation, and three sites represented high-input continuous maize monocropping. Representative soil samples were taken, and the AMF spores present were morphologically identified and counted. The same soil samples also served as inocula for “AMF trap cultures” with Plantago lanceolata, Trifolium pratense, and Lolium perenne. These trap cultures were established in pots in a greenhouse, and AMF root colonization and spore formation were monitored over 8 months. For the field samples, the numbers of AMF spores and species were highest in the grasslands, lower in the low- and moderate-input arable lands, and lowest in the lands with intensive continuous maize monocropping. Some AMF species occurred at all sites (“generalists”); most of them were prevalent in the intensively managed arable lands. Many other species, particularly those forming sporocarps, appeared to be specialists for grasslands. Only a few species were specialized on the arable lands with crop rotation, and only one species was restricted to the high-input maize sites. In the trap culture experiment, the rate of root colonization by AMF was highest with inocula from the permanent grasslands and lowest with those from the high-input monocropping sites. In contrast, AMF spore formation was slowest with the former inocula and fastest with the latter inocula. In conclusion, the increased land use intensity was correlated with a decrease in AMF species richness and with a preferential selection of species that colonized roots slowly but formed spores rapidly.

Journal ArticleDOI
TL;DR: In this article, a nomenclature for restriction endonucleases, DNA methyltransferases, homing endon nucleases and related genes and gene products is described.
Abstract: A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for naming the putative genes found by sequence analysis of microbial genomes.

Journal ArticleDOI
TL;DR: A spin-field-effect transistor based on spin-orbit coupling of both the Rashba and the Dresselhaus types is proposed, which is tolerant against spin-independent scattering processes and the requirement of strictly ballistic transport can be relaxed.
Abstract: We propose a spin-field-effect transistor based on spin-orbit coupling of both the Rashba and the Dresselhaus types. Different from earlier proposals, spin transport through our device is tolerant against spin-independent scattering processes. Hence the requirement of strictly ballistic transport can be relaxed. This follows from a unique interplay between the Dresselhaus and the Rashba coupling; these can be tuned to have equal strengths, leading to k-independent eigenspinors even in two dimensions. We discuss two-dimensional devices as well as quantum wires. In the latter, our setup presents strictly parabolic dispersions which avoids complications from anticrossings of different bands.

Journal ArticleDOI
TL;DR: The timed up and go test is recommended as a screening tool to determine whether an in-depth mobility assessment and early intervention, such as prescription of a walking aid, home visit or physiotherapy, is necessary.
Abstract: Background: physical mobility testing is an essential component of the geriatric assessment. The timed up and go test measures basic mobility skills including a sequence of functional manoeuvres used in everyday life. Objectives: to create a practical cut-off value to indicate normal versus below normal timed up and go test performance by comparing test performance of community-dwelling and institutionalised elderly women. Setting and participants: 413 community-dwelling and 78 institutionalised mobile elderly women (age range 65–85 years) were enrolled in a cross-sectional study. Measurements: timed up and go test duration, residential and mobility status, age, height, weight and body mass index were documented. Results: 92% of community-dwelling elderly women performed the timed up and go test in less than 12 seconds and all community-dwelling women had times below 20 seconds. In contrast only 9% of institutionalised elderly women performed the timed up and go test in less than 12 seconds, 42% were below 20 seconds, 32% had results between 20 and 30 seconds and 26% were above 30 seconds. The 10 th –90 th percentiles for timed up and go test performance were 6.0–11.2 seconds for community-dwelling and 12.7–50.1 seconds for institutionalised elderly women. When stratifying participants according to mobility status, the timed up and go test duration increased significantly with decreasing mobility (Kruskall-Wallis-test: p-0.0001). Linear regression modelling identified residential status (p-0.0001) and physical mobility status (p-0.0001) as significant predictors of timed up and go performance. This model predicted 54% of total variation of timed up and go test performance. Conclusion: residential and mobility status were identified as the strongest predictors of timed up and go test performance. We recommend the timed up and go test as a screening tool to determine whether an in-depth mobility assessment and early intervention, such as prescription of a walking aid, home visit or physiotherapy, is necessary. Community-dwelling elderly women between 65 and 85 years of age should be able to perform the timed up and go test in 12 seconds or less.

Journal ArticleDOI
TL;DR: Metabolic labeling with 5-bromouridine 5′-triphosphate in the presence of actinomycin D revealed that the membranous web is the site of viral RNA synthesis and therefore represents the replication complex of HCV.
Abstract: Formation of a membrane-associated replication complex, composed of viral proteins, replicating RNA, and altered cellular membranes, is a characteristic feature of plus-strand RNA viruses. Here, we demonstrate the presence of a specific membrane alteration, designated the membranous web, that contains hepatitis C virus (HCV) nonstructural proteins, as well as viral plus-strand RNA, in Huh-7 cells harboring autonomously replicating subgenomic HCV RNAs. Metabolic labeling with 5-bromouridine 5'-triphosphate in the presence of actinomycin D revealed that the membranous web is the site of viral RNA synthesis and therefore represents the replication complex of HCV.

Journal ArticleDOI
TL;DR: Structural work has now begun to shed some light onto the complex fine tuning of structure and function in these fibrous, coiled coil forming multidomain proteins and their contribution to cellular physiology and gene regulation.
Abstract: The superfamily of intermediate filament (IF) proteins contains at least 65 distinct proteins in man, which all assemble into approximately 10 nm wide filaments and are principal structural elements both in the nucleus and the cytoplasm with essential scaffolding functions in metazoan cells. At present, we have only circumstantial evidence of how the highly divergent primary sequences of IF proteins lead to the formation of seemingly similar polymers and how this correlates with their function in individual cells and tissues. Point mutations in IF proteins, particularly in lamins, have been demonstrated to lead to severe, inheritable multi-systemic diseases, thus underlining their importance at several functional levels. Recent structural work has now begun to shed some light onto the complex fine tuning of structure and function in these fibrous, coiled coil forming multidomain proteins and their contribution to cellular physiology and gene regulation.

Journal ArticleDOI
TL;DR: The classical view that deciduous trees rely more on C-reserves than evergreen trees, seems unwarranted or has lost its justification due to the greater than 30% increase in atmospheric CO 2 concentrations over the last 150 years.
Abstract: The current carbon supply status of temperate forest trees was assessed by analysing the seasonal variation of nonstructural carbohydrate (NSC) concentrations in leaves, branch wood and stem sapwood of 10 tree species (six deciduous broad-leafed, one deciduous conifer and three evergreen conifer trees) in a temperate forest that is approximately 100 years old. In addition, all woody tissue was analysed for lipids (acylglycerols). The major NSC fractions were starch, sucrose, glucose and fructose, with other carbohydrates (e.g. raffinose and stachyose) and sugar alcohols (cyclitols and sorbitol) playing only a minor quantitative role. The radial distribution of NSC within entire stem cores, assessed here for the first time in a direct interspecific comparison, revealed large differences in the size of the active sapwood fraction among the species, reflecting the specific wood anatomy (ring-porous versus diffuse-porous xylem). The mean minimum NSC concentrations in branch wood during the growing season was 55% of maximum, and even high NSC concentrations were maintained during times of extensive fruit production in masting Fagus sylvestris . The NSC in stem sapwood varied very little throughout the season (cross species mean never below 67% of maximum), and the small reductions observed were not significant for any of the investigated species. Although some species contained substantial quantities of lipids in woody tissues (‘fat trees’; Tilia , Pinus , Picea , Larix ), the lipid pools did not vary significantly across the growing season in any species. On average, the carbon stores of deciduous trees would permit to replace the whole leave canopy four times. These data imply that there is not a lot of leeway for a further stimulation of growth by ongoing atmospheric CO 2 enrichment. The classical view that deciduous trees rely more on C-reserves than evergreen trees, seems unwarranted or has lost its justification due to the greater than 30% increase in atmospheric CO 2 concentrations over the last 150 years.

Journal ArticleDOI
TL;DR: Eosinophilic esophagitis, a primary and chronic disease restricted to the esophagus, leads to persistent dysphagia and structural esophageal alterations but does not impact the nutritional state.

Journal Article
TL;DR: Results indicate preservation of the link between POU5F1 and pluripotency, as reported during normal development, after malignant transformation of GCT and the histological heterogeneity of this cancer.
Abstract: Human germ cell tumors (GCTs) may have variable histology and clinical behavior, depending on factors such as sex of the patient, age at clinical diagnosis, and anatomical site of the tumor. Some types of GCT, i.e., the seminomas/germinomas/dysgerminomas and embryonal carcinomas (the stem cell component of nonseminomas), have pluripotent potential, which is demonstrated by their capacity to differentiate into somatic and/or extraembryonic elements. Although embryonal carcinoma cells are intrinsically pluripotent, seminoma/germinoma/dysgerminoma cells, as well as their precursor carcinoma in situ/gonadoblastoma cells, have the phenotype of early germ cells that can be activated to pluripotency. The other types of GCT (teratomas and yolk sac tumors of infants and newborn, dermoid cyst of the ovary, and spermatocytic seminoma of elderly) are composed of (fully) differentiated tissues and lack the appearance of undifferentiated and pluripotent stem cells. OCT3/4, a transcription factor also known as OTF3 and POU5F1, is involved in regulation of pluripotency during normal development and is detectable in embryonic stem and germ cells. We analyzed the presence of POU5F1 in GCT and other tumor types using immunohistochemistry. The protein was consistently detected in carcinoma in situ/gonadoblastoma, seminomas/germinoma/dysgerminoma, and embryonal carcinoma but not in the various types of differentiated nonseminomas. Multitumor tissue microarray analysis covering >100 different tumor categories and 3600 individual cancers verified that POU5F1 expression is specific for particular subtypes of GCT of adults. No protein was observed in GCT of newborn and infants, spermatocytic seminomas, and the various tumors of nongerm cell origin. In addition, no difference in staining pattern was found in chemosensitive and chemoresistant GCT of adults. These results indicate preservation of the link between POU5F1 and pluripotency, as reported during normal development, after malignant transformation. Therefore, POU5F1 immunohistochemistry is an informative diagnostic tool for pluripotent GCT and offers new insights into the histological heterogeneity of this cancer.

Journal ArticleDOI
TL;DR: This is the first semi-empirical model of a higher order structure of a GPCR in native membranes, and it has profound implications for the understanding of how this receptor interacts with partner proteins.

Journal ArticleDOI
TL;DR: Findings indicate that TOR also controls the growth of non-proliferating cells, such as neurons and muscle cells, and by associating with regulatory proteins and inhibiting phosphatases, controls the activity of multiphosphorylated effectors.
Abstract: TOR--a highly conserved atypical protein kinase and the 'target of rapamycin', an immunosuppressant and anti-cancer drug--controls cell growth TOR controls the growth of proliferating yeast, fly and mammalian cells in response to nutrients Recent findings, however, indicate that TOR also controls the growth of non-proliferating cells, such as neurons and muscle cells Furthermore, TOR, by associating with regulatory proteins and inhibiting phosphatases, controls the activity of multiphosphorylated effectors

Journal ArticleDOI
TL;DR: In this article, the authors investigated whether differences in firm-specific corporate governance also help to explain expected returns in a cross-section of firms within a single jurisdiction, and found a positive relationship between the CGR and firm value.
Abstract: Recent empirical work shows that a better legal environment leads to lower expected rates of return in an international cross-section of countries. This paper investigates whether differences in firm-specific corporate governance also help to explain expected returns in a cross-section of firms within a single jurisdiction. Constructing a corporate governance rating (CGR) for German firms, we document a positive relationship between the CGR and firm value. In addition, there is strong evidence that expected returns are negatively correlated with the CGR, if dividend yields and price-earnings ratios are used as proxies for the cost of capital. Most results are robust for endogeneity, with causation running from corporate governance practices to firm fundamentals. Finally, an investment strategy that bought high-CGR firms and shorted low-CGR firms would have earned abnormal returns of around 12 percent on an annual basis during the sample period. We rationalize the empirical evidence with lower agency costs and/or the removal of certain governance malfunctions for the high-CGR firms.

Journal ArticleDOI
01 Dec 2003-Diabetes
TL;DR: The increases in PGC-1 and PPAR-alpha levels reported in this study may play an important role in the changes in muscle mitochondria content, oxidative phenotype, and sensitivity to insulin known to be induced by endurance training.
Abstract: The peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PGC-1) can induce mitochondria biogenesis and has been implicated in the development of oxidative type I muscle fibers. The PPAR isoforms α, β/δ, and γ control the transcription of genes involved in fatty acid and glucose metabolism. As endurance training increases skeletal muscle mitochondria and type I fiber content and fatty acid oxidative capacity, our aim was to determine whether these increases could be mediated by possible effects on PGC-1 or PPAR-α, -β/δ, and -γ. Seven healthy men performed 6 weeks of endurance training and the expression levels of PGC-1 and PPAR-α, -β/δ, and -γ mRNA as well as the fiber type distribution of the PGC-1 and PPAR-α proteins were measured in biopsies from their vastus lateralis muscle. PGC-1 and PPAR-α mRNA expression increased by 2.7- and 2.2-fold (P

Journal ArticleDOI
01 Sep 2003
TL;DR: A method for photo‐realistic animation that can be applied to any face shown in a single image or a video, which allows for head rotations and speech in the original sequence, but neither of these motions is required.
Abstract: This paper presents a method for photo-realistic animation of any face shown in a single image or a video. The technique does not require example data of the person’s mouth movements, and the image to be animated is not restricted in pose and illumination. Video reanimation allows for head rotations and speech in the original sequence, yet neither of these motions is required. In order to animate novel faces, the system transfers mouth movements and expressions across individuals, based a common representation of different identities and facial expressions in a vector space of 3D shapes and textures. This space is computed from 3D scans of different neutral faces, and scans of facial expressions. The 3D model’s versatility with respect to pose and illumination is conveyed to photo-realistic image and video processing by a framework of analysis and synthesis algorithms: The system automatically estimates 3D shape, pose and other rendering parameters from single images, and tracks head pose and mouth movements in video. Reanimated with new mouth movements, the 3D face is rendered into the original images.

Journal ArticleDOI
TL;DR: Both myoglobin and creatin kinase could be detected independently using cantilevers functionalized with the corresponding antibodies, in unspecific protein background, and this approach permits the use of up to seven different antigen–antibody reactions simultaneously, including an additional thermomechanical and chemical in situ reference.
Abstract: We demonstrate continuous label-free detection of two cardiac biomarker proteins (creatin kinase and myoglobin) using an array of microfabricated cantilevers functionalized with covalently anchored anti-creatin kinase and anti-myoglobin antibodies. This method allows biomarker proteins to be detected via measurement of surface stress generated by antigen–antibody molecular recognition. Reference cantilevers are used to eliminate thermal drifts, undesired chemical reactions and turbulences from injections of liquids by calculating differential deflection signals with respect to sensor cantilevers. The sensitivity achieved for myoglobin detection is below 20 µg ml−1. Both myoglobin and creatin kinase could be detected independently using cantilevers functionalized with the corresponding antibodies, in unspecific protein background. This approach permits the use of up to seven different antigen–antibody reactions simultaneously, including an additional thermomechanical and chemical in situ reference. Applications lie in the field of early and rapid diagnosis of acute myocardial infarction.

Journal ArticleDOI
03 Apr 2003-Oncogene
TL;DR: Insight is provided into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate as determined by both RT–PCR and Western analysis.
Abstract: Claudins are transmembrane proteins that seal tight junctions, and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets However, their role in cancer progression remains largely unexplored Here, we report that Claudin-7 (CLDN-7) expression is lower in invasive ductal carcinomas (IDC) of the breast than in normal breast epithelium, as determined by both RT-PCR (9/10) and Western analysis (6/8) Immunohistochemical (IHC) analysis of ductal carcinoma in situ (DCIS) and IDC showed that the loss of CLDN-7 expression correlated with histological grade in both DCIS (P<0001, n=38) and IDC (P=0014, n=31), occurring predominantly in high-grade (Nuclear and Elston grade 3) lesions Tissue array analysis of 355 IDC cases further confirmed the inverse correlation between CLDN-7 expression and histological grade (P=003) This pattern of expression is consistent with the biological function of CLDN-7, as greater discohesion is typically observed in high-grade lesions In line with this observation, by IHC analysis, CLDN-7 expression was lost in the vast majority (13/17) of cases of lobular carcinoma in situ, which is defined by cellular discohesion In fact, inducing disassociation of MCF-7 and T47D cells in culture by treating with HGF/scatter factor resulted in a loss of CLDN-7 expression within 24 h Silencing of CLDN-7 expression correlated with promoter hypermethylation as determined by methylation-specific PCR (MSP) and nucleotide sequencing in breast cancer cell lines (3/3), but not in IDCs (0/5) In summary, these studies provide insight into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate

Journal ArticleDOI
TL;DR: In this paper, a review of recent advances in nuclear structure modeling has led to improved descriptions of astrophysically important weak-interaction processes and their applications to hydrostatic solar and stellar burning, to slow and rapid neutron capture processes, to neutrino nucleosynthesis, and to explosive hydrogen burning.
Abstract: Recent experimental data and progress in nuclear structure modeling have led to improved descriptions of astrophysically important weak-interaction processes. This review discusses these advances and their applications to hydrostatic solar and stellar burning, to the slow and rapid neutron-capture processes, to neutrino nucleosynthesis, and to explosive hydrogen burning. Special emphasis is given to the weak-interaction processes associated with core-collapse supernovae. Despite significant progress, improvements in the modeling of these processes are still warranted and are expected to come from future radioactive ion-beam facilities.

Journal ArticleDOI
TL;DR: In this paper, a large-scale 3D model of the Galactic extinction is presented based on the Galactic dust distribution model of Drimmel & Spergel (2001), and the extinction A V to any point within the Galactic disk can be quickly deduced using a set of three-dimensional Cartesian grids.
Abstract: A large-scale three-dimensional model of Galactic extinction is presented based on the Galactic dust distribution model of Drimmel & Spergel (2001). The extinction A V to any point within the Galactic disk can be quickly deduced using a set of three-dimensional Cartesian grids. Extinctions from the model are compared to empirical extinction measures, including lines-of-sight in and near the Galactic plane using optical and NIR extinction measures: in particular we show how extinction can be derived from NIR color-magnitude diagrams in the Galactic plane to a distance of 8 kiloparsec.