Showing papers by "University of Tübingen published in 2003"
TL;DR: It is shown that organ formation in Arabidopsis involves dynamic gradients of the signaling molecule auxin with maxima at the primordia tips, which suggest that PIN-dependent, local auxin gradients represent a common module for formation of all plant organs, regardless of their mature morphology or developmental origin.
2,410 citations
TL;DR: The results indicate how the establishment of cell polarity, polar auxin efflux and local auxin response result in apical–basal axis formation of the embryo, and thus determine the axiality of the adult plant.
Abstract: Axis formation occurs in plants, as in animals, during early embryogenesis. However, the underlying mechanism is not known. Here we show that the first manifestation of the apical-basal axis in plants, the asymmetric division of the zygote, produces a basal cell that transports and an apical cell that responds to the signalling molecule auxin. This apical-basal auxin activity gradient triggers the specification of apical embryo structures and is actively maintained by a novel component of auxin efflux, PIN7, which is located apically in the basal cell. Later, the developmentally regulated reversal of PIN7 and onset of PIN1 polar localization reorganize the auxin gradient for specification of the basal root pole. An analysis of pin quadruple mutants identifies PIN-dependent transport as an essential part of the mechanism for embryo axis formation. Our results indicate how the establishment of cell polarity, polar auxin efflux and local auxin response result in apical-basal axis formation of the embryo, and thus determine the axiality of the adult plant.
1,767 citations
TL;DR: A hydraulic model of the water exchange between the Red Sea and the world ocean is used to derive the sill depth—and hence global sea level—over the past 470,000 years, finding that sea-level changes of up to 35 m occurred, coincident with abrupt changes in climate.
Abstract: The last glacial cycle was characterized by substantial millennial-scale climate fluctuations1,2,3,4,5, but the extent of any associated changes in global sea level (or, equivalently, ice volume) remains elusive. Highstands of sea level can be reconstructed from dated fossil coral reef terraces6,7, and these data are complemented by a compilation of global sea-level estimates based on deep-sea oxygen isotope ratios at millennial-scale resolution8 or higher1. Records based on oxygen isotopes, however, contain uncertainties in the range of ±30 m, or ±1 °C in deep sea temperature9,10. Here we analyse oxygen isotope records from Red Sea sediment cores to reconstruct the history of water residence times in the Red Sea. We then use a hydraulic model of the water exchange between the Red Sea and the world ocean to derive the sill depth—and hence global sea level—over the past 470,000 years (470 kyr). Our reconstruction is accurate to within ±12 m, and gives a centennial-scale resolution from 70 to 25 kyr before present. We find that sea-level changes of up to 35 m, at rates of up to 2 cm yr-1, occurred, coincident with abrupt changes in climate.
1,485 citations
TL;DR: It is shown that proteins involved in auxin transport regulate phyllotaxis, and data indicate that auxin is transported upwards into the meristem through the epidermis and the outermostMeristem cell layer.
Abstract: The regular arrangement of leaves around a plant's stem, called phyllotaxis, has for centuries attracted the attention of philosophers, mathematicians and natural scientists; however, to date, studies of phyllotaxis have been largely theoretical. Leaves and flowers are formed from the shoot apical meristem, triggered by the plant hormone auxin. Auxin is transported through plant tissues by specific cellular influx and efflux carrier proteins. Here we show that proteins involved in auxin transport regulate phyllotaxis. Our data indicate that auxin is transported upwards into the meristem through the epidermis and the outermost meristem cell layer. Existing leaf primordia act as sinks, redistributing auxin and creating its heterogeneous distribution in the meristem. Auxin accumulation occurs only at certain minimal distances from existing primordia, defining the position of future primordia. This model for phyllotaxis accounts for its reiterative nature, as well as its regularity and stability.
1,420 citations
TL;DR: The IBIS telescope as mentioned in this paper is the high angular resolution gamma-ray imager on-board the INTEGRAL Observatory, which was successfully launched from Baikonur (Kazakhstan) the 17th of October 2002.
Abstract: The IBIS telescope is the high angular resolution gamma-ray imager on-board the INTEGRAL Observatory, suc- cessfully launched from Baikonur (Kazakhstan) the 17th of October 2002. This medium size ESA project, planned for a 2 year mission with possible extension to 5, is devoted to the observation of the gamma-ray sky in the energy range from 3 keV to 10 MeV (Winkler 2001). The IBIS imaging system is based on two independent solid state detector arrays optimised for low (15 1000 keV) and high (0:175 10:0 MeV) energies surrounded by an active VETO System. This high eciency shield is essential to minimise the background induced by high energy particles in the highly excentric out of van Allen belt orbit. A Tungsten Coded Aperture Mask, 16 mm thick and1 squared meter in dimension is the imaging device. The IBIS telescope will serve the scientific community at large providing a unique combination of unprecedented high energy wide field imaging capability coupled with broad band spectroscopy and high resolution timing over the energy range from X to gamma rays. To date the IBIS telescope is working nominally in orbit since more than 9 month.
1,138 citations
TL;DR: It is demonstrated that GNOM localizes to endosomes and is required for their structural integrity and suggested that ARF-GEFs regulate specific endosomal trafficking pathways.
1,097 citations
Seconda Università degli Studi di Napoli1, University of Graz2, University of Rome Tor Vergata3, University of Vienna4, University of Naples Federico II5, University of Regensburg6, University of Sydney7, University of L'Aquila8, University of Miami9, University of Ljubljana10, University of Tübingen11, University of Geneva12, University of Buenos Aires13, University of Florence14, Medical College of Wisconsin15, University of Connecticut16, Memorial Sloan Kettering Cancer Center17, Cornell University18, University of Lübeck19, University of Barcelona20, University of Siena21, Rutgers University22, Shinshu University23, University of Modena and Reggio Emilia24, Keio University25, Ludwig Maximilian University of Munich26, New York University27
TL;DR: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.
Abstract: Background: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. Objective: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Methods: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. κ Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Results: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean κ value: 0.53). Conclusion: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions. (J Am Acad Dermatol 2003;48:679-93.) J Am Acad Dermatol 2003;48:679-93.
971 citations
27 Oct 2003
TL;DR: First results on real data demonstrate, that the normal distributions transform algorithm is capable to map unmodified indoor environments reliable and in real time, even without using odometry data.
Abstract: Matching 2D range scans is a basic component of many localization and mapping algorithms. Most scan match algorithms require finding correspondences between the used features, i.e. points or lines. We propose an alternative representation for a range scan, the normal distributions transform. Similar to an occupancy grid, we subdivide the 2D plane into cells. To each cell, we assign a normal distribution, which locally models the probability of measuring a point. The result of the transform is a piecewise continuous and differentiable probability density, that can be used to match another scan using Newton's algorithm. Thereby, no explicit correspondences have to be established. We present the algorithm in detail and show the application to relative position tracking and simultaneous localization and map building (SLAM). First results on real data demonstrate, that the algorithm is capable to map unmodified indoor environments reliable and in real time, even without using odometry data.
944 citations
TL;DR: Evidence is presented that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages and that lysophosphatidylcholine was released from apoptotic Cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2).
890 citations
TL;DR: Studies on auxin transport, as well as tracing the intracellular movement of its molecular components, have suggested a possible scenario to explain how growth plasticity is conferred at the cellular and molecular level.
682 citations
TL;DR: A specialized database (DB) for Arabidopsis membrane proteins, ARAMEMNON, was designed that facilitates the interpretation of gene and protein sequence data by integrating features that are presently only available from individual sources.
Abstract: A specialized database (DB) for Arabidopsis membrane proteins, ARAMEMNON, was designed that facilitates the interpretation of gene and protein sequence data by integrating features that are presently only available from individual sources Using several publicly available prediction programs, putative integral membrane proteins were identified among the approximately 25,500 proteins in the Arabidopsis genome DBs By averaging the predictions from seven programs, approximately 6,500 proteins were classified as transmembrane (TM) candidate proteins Some 1,800 of these contain at least four TM spans and are possibly linked to transport functions The ARAMEMNON DB enables direct comparison of the predictions of seven different TM span computation programs and the predictions of subcellular localization by eight signal peptide recognition programs A special function displays the proteins related to the query and dynamically generates a protein family structure As a first set of proteins from other organisms, all of the approximately 700 putative membrane proteins were extracted from the genome of the cyanobacterium Synechocystis sp and incorporated in the ARAMEMNON DB The ARAMEMNON DB is accessible at the URL http://aramemnonbotanikuni-koelnde
TL;DR: This conceptual framework calls for a new view on field data from bats orienting and foraging in different types of habitats according to the ecological constraints in which foraging bats operate, four distinct functional groups or guilds within each group, signal design and echolocation behavior are rather similar.
Abstract: Field research on echolocation behavior in bats has emphasized studies of food acquisition, and the adaptive value of sonar signal design as been considered largely in the context of foraging. However, echolocation tasks related to spatial orientation also differ among bats and are relevant to understanding signal structure. Here, we argue that the evolution of echolocation in bats is characterized by two key innovations: first, the evolution of echolocation for spatial orientation and, second, a later transition for prey acquisition. This conceptual framework calls for a new view on field data from bats orienting and foraging in different types of habitats. According to the ecological constraints in which foraging bats operate, four distinct functional groups or guilds can be defined. Within each group, signal design and echolocation behavior are rather similar.
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.
TL;DR: A short period of active motor training is more effective than passive motor training in eliciting performance improvements and cortical reorganization, consistent with the concept of a pivotal role for voluntary drive in motor learning and neurorehabilitation.
Abstract: Summary Motor training consisting of voluntary movements leads to performance improvements and results in characteristic reorganizational changes in the motor cortex. It has been proposed that repetition of passively elicited movements could also lead to improvements in motor performance. In this study, we compared behavioural gains, changes in functional MRI (fMRI) activation in the contralateral primary motor cortex (cM1) and in motor cortex excitability measured with transcranial magnetic stimulation (TMS) after a 30 min training period of either voluntarily (active) or passively (passive) induced wrist movements, when alertness and kinematic aspects of training were controlled. During active training, subjects were instructed to perform voluntary wrist flexion‐extension movements of a specified duration (target window 174‐186 ms) in an articulated splint. Passive training consisted of wrist flexion‐ extension movements elicited by a torque motor, of the same amplitude and duration range as in the active task. fMRI activation and TMS parameters of motor cortex excitability were measured before and after each training type. Motor performance, measured as the number of movements that hit the target window duration, was significantly better after active than after passive training. Both active and passive movements performed during fMRI measurements activated cM1. Active training led to more prominent increases in (i) fMRI activation of cM1; (ii) recruitment curves (TMS); and (iii) intracortical facilitation (TMS) than passive training. Therefore, a short period of active motor training is more effective than passive motor training in eliciting performance improvements and cortical reorganization. This result is consistent with the concept of a pivotal role for voluntary drive in motor learning and neurorehabilitation.
TL;DR: In this article, the effect of water vapour in CO sensing by using Pd doped SnO2 sensors realized in thick film technology was investigated, and the results of phenomenological and spectroscopic measurement techniques, all of them obtained under working conditions for sensors, were combined with modelling in order to derive conclusions able to be generalized to the field of metal oxide based gas sensors.
Abstract: This paper investigates the effect of water vapour in CO sensing by using Pd doped SnO2 sensors realized in thick film technology as an example of the basic understanding of sensing mechanisms applied to sensors. The results of phenomenological and spectroscopic measurement techniques, all of them obtained under working conditions for sensors, were combined with modelling in order to derive conclusions able to be generalized to the field of metal oxide based gas sensors. The techniques employed were: dc conductance, ac impedance spectroscopy, work function (by using the Kelvin probe method), catalytic conversion and diffuse reflectance infrared Fourier transform measurements. The most important conclusion is that the different parts of the sensor (sensing layer, electrodes, substrate) are all influencing the gas detection and their role has to be taken into consideration when one attempts to understand how a sensor works.
TL;DR: In nondiabetic individuals, high adiponectin predicts increased insulin sensitivity, independent of low body fat mass and affects not only insulin-stimulated glucose disposal but also lipoprotein metabolism and insulin-mediated suppression of postprandial FFA release.
Abstract: In animals, the adipocyte-derived hormone adiponectin has been shown to improve insulin sensitivity, a key factor in the pathogenesis of type 2 diabetes. In Pima Indians, high plasma adiponectin levels are associated with increased insulin sensitivity and reduced risk of type 2 diabetes. It is unclear whether this is also the case in white individuals and whether an additional beneficial effect on lipid metabolism exists. We therefore analyzed in nondiabetic individuals the associations between plasma adiponectin concentrations and insulin sensitivity measured by a euglycemic-hyperinsulinemic clamp (n = 262) and estimated by an oral glucose tolerance test (OGTT; n = 636) and serum lipid parameters using correlational analysis. Plasma adiponectin concentrations were positively correlated with insulin sensitivity, both measured with the clamp (r = 0.28, P = 0.0015 in women; r = 0.42, P < 0.0001 in men) and estimated from the OGTT (r = 0.37, P < 0.0001 in women; r = 0.41, P < 0.0001 in men) before and after adjusting for sex and percentage of body fat (all P < 0.001). Fasting triglycerides and the free fatty acid (FFA) concentrations during the OGTT (area under the curve) and at 120 min were negatively correlated in both women and men, whereas HDL was positively correlated with plasma adiponectin concentrations (all P < 0.004). Most notable, these relationships remained significant after adjusting for insulin sensitivity of glucose disposal in addition to sex and percentage of body fat (all P < 0.05). In conclusion, high adiponectin predicts increased insulin sensitivity. This relationship is independent of low body fat mass and affects not only insulin-stimulated glucose disposal but also lipoprotein metabolism and insulin-mediated suppression of postprandial FFA release. This suggests pleiotropic insulin sensitizing effects of adiponectin in humans.
TL;DR: In this article, the authors present a cross-section of the recent monograph by Newton-Stormer-Verlet-leapfrog method and its various interpretations, followed by a discussion of geometric properties: reversibility, symplecticity, volume preservation, and conservation of first integrals.
Abstract: The subject of geometric numerical integration deals with numerical integrators that preserve geometric properties of the flow of a differential equation, and it explains how structure preservation leads to an improved long-time behaviour. This article illustrates concepts and results of geometric numerical integration on the important example of the Stormer/Verlet method. It thus presents a cross-section of the recent monograph by the authors, enriched by some additional material. After an introduction to the Newton-Stormer-Verlet-leapfrog method and its various interpretations, there follows a discussion of geometric properties: reversibility, symplecticity, volume preservation, and conservation of first integrals. The extension to Hamiltonian systems on manifolds is also described. The theoretical foundation relies on a backward error analysis, which translates the geometric properties of the method into the structure of a modified differential equation, whose flow is nearly identical to the numerical method. Combined with results from perturbation theory, this explains the excellent long-time behaviour of the method: long-time energy conservation, linear error growth and preservation of invariant tori in near-integrable systems, a discrete virial theorem, preservation of adiabatic invariants.
TL;DR: On the basis of this early analysis of single-center studies, the use of cerebral protection devices appears to reduce thromboembolic complications during CAS and should be taken into account before the initiation of further randomized trials comparing CAS with carotid endarterectomy.
Abstract: Background— Carotid angioplasty and stenting (CAS) is increasingly being used for treatment of symptomatic and asymptomatic carotid artery disease (CAD). To evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during CAS, we conducted a systematic review of studies reporting on the incidence of minor stroke, major stroke, or death within 30 days after CAS. Summary of Review— We searched for studies published between January 1990 and June 2002 by means of a PubMed search and a cumulative review of reference lists of all relevant publications. In 2357 patients a total of 2537 CAS procedures had been performed without protection devices, and in 839 patients 896 CAS procedures had been performed with protection devices. Both groups were similar with respect to age, sex distribution, cerebrovascular risk factors, and indications for CAS. In many studies the periprocedural complication rates had not been presented separately for patients with symptomatic and asymptomat...
TL;DR: Results on the export of GSH and GSSG from brain cells as well as on the functions of extracellular GSH in the brain are reviewed and implications of disturbed GSH pathways in brain for neurodegenerative diseases will be discussed.
Abstract: The antioxidant glutathione (GSH) is essential for the cellular detoxification of reactive oxygen species in brain cells. A compromised GSH system in the brain has been connected with the oxidative stress occuring in neurological diseases. Recent data demonstrate that besides intracellular functions GSH has also important extracellular functions in brain. In this respect astrocytes appear to play a key role in the GSH metabolism of the brain, since astroglial GSH export is essential for providing GSH precursors to neurons. Of the different brain cell types studied in vitro only astrocytes release substantial amounts of GSH. In addition, during oxidative stress astrocytes efficiently export glutathione disulfide (GSSG). The multidrug resistance protein 1 participates in both the export of GSH and GSSG from astrocytes. This review focuses on recent results on the export of GSH and GSSG from brain cells as well as on the functions of extracellular GSH in the brain. In addition, implications of disturbed GSH pathways in brain for neurodegenerative diseases will be discussed.
TL;DR: This work shows that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen P. aeruginosa.
Abstract: Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen.
TL;DR: It is reported that leukemia cells from patients variously express MIC and ULBP molecules on the cell surface with MICA most frequently detected, and determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies.
TL;DR: Compared to cisplatin, carboplatin has inferior efficacy in germ-cell tumour, head and neck cancer and bladder and oesophageal carcinoma, whereas both drugs seem to have comparable efficacy in advanced non-small cell and small cell lung cancer as well as ovarian cancer.
Abstract: Since the introduction of platinum-based combination chemotherapy, particularly cisplatin, the outcome of the treatment of many solid tumours has changed. The leading platinum compounds in cancer chemotherapy are cisplatin, carboplatin and oxaliplatin. They share some structural similarities; however, there are marked differences between them in therapeutic use, pharmacokinetics and adverse effects profiles [1-4]. Compared to cisplatin, carboplatin has inferior efficacy in germ-cell tumour, head and neck cancer and bladder and oesophageal carcinoma, whereas both drugs seem to have comparable efficacy in advanced non-small cell and small cell lung cancer as well as ovarian cancer [5-7]. Oxaliplatin belongs to the group of diaminocyclohexane platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid [8,9]. Other platinum compounds such as oral JM216, ZD0473, BBR3464 and SPI-77, which is a pegylated lipo...
TL;DR: There has been a marked increase in the prevalence and incidence of urolithiasis in Germany within the last 22 years, probably results from improvements in clinical-diagnostic procedures, changes in nutritional and environmental factors and a general apathy towards metabolic clarification and metaphylaxis.
TL;DR: In this article, a selective review examines theoretical perspectives on the role of on-demand help in interactive learning environments, reviews literature on the relations between help seeking and learning in ILEs, and identifies reasons for the lack of effective help use.
Abstract: Many interactive learning environments (ILEs) offer on-demand help, intended to positively influence learning. Recent studies report evidence that although effective help-seeking behavior in ILEs is related to better learning outcomes, learners are not using help facilities effectively. This selective review (a) examines theoretical perspectives on the role of on-demand help in ILEs, (b) reviews literature on the relations between help seeking and learning in ILEs, and (c) identifies reasons for the lack of effective help use. We review the effect of system-related factors, of student-related factors, and of interactions between these factors. The interaction between metacognitive skills and cognitive factors is important for appropriate help seeking, as are a potentially large space of system-related factors as well as interactions among learner- and system-related factors. We suggest directions for future research.
TL;DR: Tumor lymphangiogenesis is revealed as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma.
Abstract: Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from nonmetastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma.
TL;DR: Examples of MEA biosensor applications are described that have been developed for drug screening and discovery and safety pharmacology in the field of cardiac and neural research and biophysical basics of recording and concepts for analysis of extracellular electrical signals are presented.
Abstract: Electrical activity of electrogenic cells in neuronal and cardiac tissue can be recorded by means of microelectrode arrays (MEAs) that offer the unique possibility for non-invasive extracellular recording from as many as 60 sites simultaneously. Since its introduction 30 years ago, the technology and the related culture methods for electrophysiological cell and tissue assays have been continually improved and have found their way into many academic and industrial laboratories. Currently, this technology is attracting increased interest owing to the industrial need to screen selected compounds against ion channel targets in their native environment at organic, cellular, and sub-cellular level. As the MEA technology can be applied to any electrogenic tissue (i.e., central and peripheral neurons, heart cells, and muscle cells), the MEA biosensor is an ideal in vitro system to monitor both acute and chronic effects of drugs and toxins and to perform functional studies under physiological or induced pathophysiological conditions that mimic in vivo damages. By recording the electrical response of various locations on a tissue, a spatial map of drug effects at different sites can be generated, providing important clues about a drug's specificity. In this survey, examples of MEA biosensor applications are described that have been developed for drug screening and discovery and safety pharmacology in the field of cardiac and neural research. Additionally, biophysical basics of recording and concepts for analysis of extracellular electrical signals are presented.
TL;DR: In this paper, the authors present the global baroclinic instability as a source for vigorous turbulence leading to angular momentum transport in Keplerian accretion disks, and demonstrate in a global simulation that these vortices tend to form out of little background noise and to be long-lasting features.
Abstract: In this paper we present the global baroclinic instability as a source for vigorous turbulence leading to angular momentum transport in Keplerian accretion disks. We show by analytical considerations and three-dimensional radiation-hydrodynamic simulations that, in particular, protoplanetary disks have a negative radial entropy gradient, which makes them baroclinic. Two-dimensional numerical simulations show that a baroclinic flow is unstable and produces turbulence. These findings are tested for numerical effects by performing a simulation with a barotropic initial condition, which shows that imposed turbulence rapidly decays. The turbulence in baroclinic disks transports angular momentum outward and creates a radially inward-bound accretion of matter. Potential energy is released, and excess kinetic energy is dissipated. Finally, the reheating of the gas supports the radial entropy gradient, forming a self-consistent process. We measure accretion rates in our two-dimensional and three-dimensional simulations of = -10-9 to -10-7 M? yr-1 and viscosity parameters of ? = 10-4 to 10-2, which fit perfectly together and agree reasonably with observations. The turbulence creates pressure waves, Rossby waves, and vortices in the (R, )-plane of the disk. We demonstrate in a global simulation that these vortices tend to form out of little background noise and to be long-lasting features, which have already been suggested to lead to the formation of planets.
TL;DR: The selective loss of claudin-3 from BBB TJs under pathological conditions such as EAE or GBM when the integrity of the BBB is compromised is demonstrated, and therefore it is suggested that claud in-3 is a central component determining the Integrity of BBB BJ TJs in vivo.
Abstract: In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB) During inflammation, BBB properties are frequently lost, resulting in brain edema To investigate whether BBB leakiness correlates with molecular changes at BBB TJs, we performed immunofluorescence stainings for TJ molecules in a mouse model of experimental autoimmune encephalomyelitis (EAE) and in human tissue with glioblastoma multiforme (GBM) In TJs of healthy CNS vessels in both mouse and man we detected occludin, ZO-1, claudin-5 and claudin-3 In EAE brain and spinal cord sections we observed the selective loss of claudin-3 immunostaining from TJs of venules surrounded by inflammatory cuffs, whereas the localization of the other TJ proteins remained unchanged In addition, selective loss of claudin-3 immunostaining was also observed in altered cerebral microvessels of human GBM Our data demonstrate the selective loss of claudin-3 from BBB TJs under pathological conditions such as EAE or GBM when the integrity of the BBB is compromised, and therefore suggest that claudin-3 is a central component determining the integrity of BBB TJs in vivo
TL;DR: It is suggested that neurofeedback was efficient in improving some of the behavioral concomitants of ADHD in children whose parents favored a nonpharmacological treatment.
Abstract: Clinical trials have suggested that neurofeedback may be efficient in treating attention- deficit /hyperactivity disorder (ADHD). We compared the effects of a 3-month electroen- cephalographic feedback program providing reinforcement contingent on the production of cortical sensorimotor rhythm (12-15 Hz) and beta1 activity (15-18 Hz) with stimulant medication. Participants were ND 34 children aged 8-12 years, 22 of which were assigned to the neurofeedback group and 12 to the methylphenidate group according to their parents' preference. Both neurofeedback and methylphenidate were associated with improvements on all subscales of the Test of Variables of Attention, and on the speed and accuracy mea- sures of the d2 Attention Endurance Test. Furthermore, behaviors related to the disorder were rated as significantly reduced in both groups by both teachers and parents on the IOWA-Conners Behavior Rating Scale. These findings suggest that neurofeedback was effi- cient in improving some of the behavioral concomitants of ADHD in children whose parents favored a nonpharmacological treatment.