Showing papers by "Wolfgang Wagner published in 2010"
TL;DR: It is found that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis in normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells.
Abstract: Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of approximately 14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8-7.4], P < 10(-10)), independently of sex, tissue type, disease state, and methylation platform. We identified a specific subset of 69 PCGT CpGs that undergo hypermethylation with age and validated this methylation signature in seven independent data sets encompassing over 900 samples, including normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells (P < 10(-5)). We find that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis. These findings shed substantial novel insights into the epigenetic effects of aging and support the view that age may predispose to malignant transformation by irreversibly stabilizing stem cell features.
801 citations
TL;DR: Overall, methylation patterns were maintained throughout both long‐term culture and aging but highly significant differences were observed at specific CpG sites, which supports the notion that replicative senescence and aging represent developmental processes that are regulated by specific epigenetic modifications.
Abstract: Within 2–3 months of in vitro culture-expansion, mesenchymal stromal cells (MSC) undergo replicative senescence characterized by cell enlargement, loss of differentiation potential and ultimate growth arrest In this study, we have analyzed DNA methylation changes upon long-term culture of MSC by using the HumanMethylation27 BeadChip microarray assessing 27 578 unique CpG sites Furthermore, we have compared MSC from young and elderly donors Overall, methylation patterns were maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites Many of these differences were observed in homeobox genes and genes involved in cell differentiation Methylation changes were verified by pyrosequencing after bisulfite conversion and compared to gene expression data Notably, methylation changes in MSC were overlapping in long-term culture and aging in vivo This supports the notion that replicative senescence and aging represent developmental processes that are regulated by specific epigenetic modifications
401 citations
TL;DR: In this paper, a triple collocation error estimation technique for assessing the relative quality of several globally available soil moisture products from active (ASCAT) and passive (AMSR-E and SSM/I) microwave sensors is proposed.
Abstract: . Understanding the error structures of remotely sensed soil moisture observations is essential for correctly interpreting observed variations and trends in the data or assimilating them in hydrological or numerical weather prediction models. Nevertheless, a spatially coherent assessment of the quality of the various globally available datasets is often hampered by the limited availability over space and time of reliable in-situ measurements. As an alternative, this study explores the triple collocation error estimation technique for assessing the relative quality of several globally available soil moisture products from active (ASCAT) and passive (AMSR-E and SSM/I) microwave sensors. The triple collocation is a powerful statistical tool to estimate the root mean square error while simultaneously solving for systematic differences in the climatologies of a set of three linearly related data sources with independent error structures. Prerequisite for this technique is the availability of a sufficiently large number of timely corresponding observations. In addition to the active and passive satellite-based datasets, we used the ERA-Interim and GLDAS-NOAH reanalysis soil moisture datasets as a third, independent reference. The prime objective is to reveal trends in uncertainty related to different observation principles (passive versus active), the use of different frequencies (C-, X-, and Ku-band) for passive microwave observations, and the choice of the independent reference dataset (ERA-Interim versus GLDAS-NOAH). The results suggest that the triple collocation method provides realistic error estimates. Observed spatial trends agree well with the existing theory and studies on the performance of different observation principles and frequencies with respect to land cover and vegetation density. In addition, if all theoretical prerequisites are fulfilled (e.g. a sufficiently large number of common observations is available and errors of the different datasets are uncorrelated) the errors estimated for the remote sensing products are hardly influenced by the choice of the third independent dataset. The results obtained in this study can help us in developing adequate strategies for the combined use of various scatterometer and radiometer-based soil moisture datasets, e.g. for improved flood forecast modelling or the generation of superior multi-mission long-term soil moisture datasets.
369 citations
TL;DR: In this paper, the authors compared the soil wetness index (SWI) derived from the Advanced SCATterometer (ASCAT) sensor onboard of the Metop satellite with the soil moisture temporal pattern derived from a continuous rainfall-runoff model (MISDc) to assess its relationship with modeled data.
Abstract: . The role and the importance of soil moisture for meteorological, agricultural and hydrological applications is widely known. Remote sensing offers the unique capability to monitor soil moisture over large areas (catchment scale) with, nowadays, a temporal resolution suitable for hydrological purposes. However, the accuracy of the remotely sensed soil moisture estimates has to be carefully checked. The validation of these estimates with in-situ measurements is not straightforward due the well-known problems related to the spatial mismatch and the measurement accuracy. The analysis of the effects deriving from assimilating remotely sensed soil moisture data into hydrological or meteorological models could represent a more valuable method to test their reliability. In particular, the assimilation of satellite-derived soil moisture estimates into rainfall-runoff models at different scales and over different regions represents an important scientific and operational issue. In this study, the soil wetness index (SWI) product derived from the Advanced SCATterometer (ASCAT) sensor onboard of the Metop satellite was tested. The SWI was firstly compared with the soil moisture temporal pattern derived from a continuous rainfall-runoff model (MISDc) to assess its relationship with modeled data. Then, by using a simple data assimilation technique, the linearly rescaled SWI that matches the range of variability of modelled data (denoted as SWI*) was assimilated into MISDc and the model performance on flood estimation was analyzed. Moreover, three synthetic experiments considering errors on rainfall, model parameters and initial soil wetness conditions were carried out. These experiments allowed to further investigate the SWI potential when uncertain conditions take place. The most significant flood events, which occurred in the period 2000–2009 on five subcatchments of the Upper Tiber River in central Italy, ranging in extension between 100 and 650 km2, were used as case studies. Results reveal that the SWI derived from the ASCAT sensor can be conveniently adopted to improve runoff prediction in the study area, mainly if the initial soil wetness conditions are unknown.
365 citations
TL;DR: Some basic physical concepts commonly used by the remote sensing community for modelling scattering and reflection processes are reviewed and the backscattering coefficient γ is recommended to use for the radiometric calibration of small-footprint full-waveform airborne laser scanners.
Abstract: Small-footprint (0.2–2 m) airborne laser scanners are lidar instruments originally developed for topographic mapping. While the first airborne laser scanners only allowed determining the range from the sensor to the target, the latest sensor generation records the complete echo waveform. The waveform provides important information about the backscattering properties of the observed targets and may be useful for geophysical parameter retrieval and advanced geometric modelling. However, to fully utilise the potential of the waveform measurements in applications, it is necessary to perform a radiometric calibration. As there are not yet calibration standards, this paper reviews some basic physical concepts commonly used by the remote sensing community for modelling scattering and reflection processes. Based purely on theoretical arguments it is recommended to use the backscattering coefficient γ , which is the backscatter cross-section normalised relative to the laser footprint area, for the radiometric calibration of small-footprint full-waveform airborne laser scanners. The presented concepts are, with some limitations, also applicable to conventional airborne laser scanners that measure the range and intensity of multiple echoes.
213 citations
TL;DR: There is a growing perception that long-term culture has to be taken into account--especially for clinical applications, and the state of replicative senescence is poorly defined by the number of population doublings or even by thenumber of passages.
Abstract: Mesenchymal stem cells (MSCs) have to be culture expanded to gain relevant cell numbers for therapeutic applications. However, within 2-3 months the proliferation rate of MSCs decays until they ultimately reach a senescent state. This is accompanied by enlarged morphology, reduced expression of surface markers, and decreased differentiation potential. So far it is only scarcely understood how long-term culture affects MSC preparations, and five processes seem to be involved: (1) MSCs are composed of different sub-populations, and due to different proliferation rates the heterogeneity changes in the course of in vitro expansion; (2) cells in culture acquire mutations and other stochastic cellular defects; (3) self-renewal of MSCs may be impaired under culture conditions, leading to gradual differentiation; (4) the number of cell divisions might be restricted (e.g., by loss of telomeres), and (5) replicative senescence might be associated with the aging process of the organism. There is a growing perception that long-term culture has to be taken into account--especially for clinical applications. On the other hand, the state of replicative senescence is poorly defined by the number of population doublings or even by the number of passages. Reliable molecular measures for cellular aging are urgently needed.
200 citations
TL;DR: In this article, satellite-based passive and active microwave measurements are evaluated for 2005-2006 against ground measurements obtained from the soil moisture network deployed in Mali (Sahel) in the framework of the African Monsoon Multidisciplinary Analysis project.
Abstract: This paper presents a comparison and an evaluation of five soil moisture products based on satellite-based passive and active microwave measurements Products are evaluated for 2005–2006 against ground measurements obtained from the soil moisture network deployed in Mali (Sahel) in the framework of the African Monsoon Multidisciplinary Analysis project It is shown that the accuracy of the soil moisture products is sensitive to the retrieval approach as well as to the sensor type (active or passive) and to the signal frequency (from 56 GHz to 188 GHz) The spatial patterns of surface soil moisture are compared between the different products at meso-scale (145° N–175° N and 2° W–1° W) A general good consistency between the different satellite soil moisture products is shown in terms of meso-scale spatial distribution, in particular after convective rainfall occurrences Comparison to ground measurement shows that although soil moisture products obtained from satellite generally over-estimate soil moisture values during the dry season, most of them capture soil moisture temporal variations in good agreement with ground station measurements
200 citations
TL;DR: MSC support proliferation as well as self‐renewal of HPC with primitive immunophenotype, and the use of early passages of MSC and genetic manipulation of proteins involved in HPC–MSC interaction might further enhance cord blood expansion on MSC.
Abstract: Mesenchymal stromal cells (MSC) have been suggested to provide a suitable cellular environment for in vitro expansion of haematopoietic stem and progenitor cells (HPC) from umbilical cord blood. In this study, we have simultaneously analysed the cell division history and immunophenotypic differentiation of HPC by using cell division tracking with carboxyfluorescein diacetate N-succinimidyl ester (CFSE). Co-culture with MSC greatly enhanced proliferation of human HPC, especially of the more primitive CD34(+)CD38(-) fraction. Without co-culture CD34 and CD133 expressions decreased after several cell divisions, whereas CD38 expression was up-regulated after some cell divisions and then diminished in fast proliferating cells. Co-culture with MSC maintained a primitive immunophenotype (CD34(+), CD133(+) and CD38(-)) for more population doublings, whereas up-regulation of differentiation markers (CD13, CD45 and CD56) in HPC was delayed to higher numbers of cell divisions. Especially MSC of early cell passages maintained CD34 expression in HPC over more cell divisions, whereas MSC of higher passages further enhanced their proliferation rate. Inhibition of mitogen-activated protein kinase 1 (MAPK1) impaired proliferation and differentiation of HPC, but not maintenance of long-term culture initiating cells. siRNA knockdown of N-cadherin and VCAM1 in feeder layer cells increased the fraction of slow dividing HPC, whereas knockdown of integrin beta 1 (ITGB1) and CD44 impaired their differentiation. In conclusion, MSC support proliferation as well as self-renewal of HPC with primitive immunophenotype. The use of early passages of MSC and genetic manipulation of proteins involved in HPC-MSC interaction might further enhance cord blood expansion on MSC.
166 citations
TL;DR: These results exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.V. level, and resulting limits on Higgs Boson production are excluded.
Abstract: We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
158 citations
TL;DR: In this paper, the accuracy of the new 25 km ASCAT derived saturation degree product by using in situ observations and the outcomes of a soil water balance model for three sites located in an inland region of central Italy was evaluated.
153 citations
08 Apr 2010
TL;DR: It is demonstrated that gene expression changes and epigenetic modifications are continuously acquired during replicative senescence in Mesenchymal stromal cells.
Abstract: Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long-term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, differentiation potential is affected, chromosomal instabilities may arise and molecular changes are acquired. Long-term culture of cell preparations might also have therapeutic consequences, although this has hardly been addressed in ongoing trials so far. Reliable therapeutic regimens necessitate quality control of cellular products. This research perspective summarizes available methods to track cellular aging of MSC. We have demonstrated that gene expression changes and epigenetic modifications are continuously acquired during replicative senescence. Molecular analysis of a suitable panel of genes might provide a robust tool to assess efficiency and safety of long-term expansion.
TL;DR: No clinically meaningful differences were found between the two treatment arms, and the primary study end point was not met, and among the patients receiving imatinib, no adverse events were reported that were either previously unknown or unexpected as a consequence of the disease.
Abstract: A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy, and first-line chemotherapy (preferably temozolomide (TMZ) containing regimen) and who have progressed despite treatment. If first-line chemotherapy did not contain TMZ, a second completed chemotherapy was acceptable. The primary efficacy parameter was progression-free survival (PFS). The primary comparison of combination therapy versus monotherapy for PFS was not significant (adjusted P = 0.56). The hazard ratio (HR) (adjusted HR = 0.93) was not clinically relevant. The median PFS for the combination arm was low at 6 weeks and similar to the median PFS in the monotherapy arm (6 weeks). The 6-month PFS for the two treatment groups was very similar (5% in the combination arm vs. 7% in the monotherapy arm). No clinically meaningful differences were found between the two treatment arms, and the primary study end point was not met. Among the patients receiving imatinib, no adverse events were reported that were either previously unknown or unexpected as a consequence of the disease.
TL;DR: In this paper, the authors compared activities of individual platelet lysate (HPL) on initial fibroblastoid colony-forming units (CFU-F), proliferation, in vitro differentiation and long-term culture.
TL;DR: A search for new heavy particles manifested as resonances in two-jet final states in 7 TeV proton-proton collisions by the LHC is presented, extending the reach of previous experiments.
Abstract: A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315 nb(-1) collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C. L. the q* mass interval 0: 30< m(q)*< 1:26 TeV, extending the reach of previous experiments.
TL;DR: In this paper, the first measurements of the W and Z/gamma*-boson production cross sections in proton-proton collisions at 7 TeV are presented using data recorded by the ATLAS experiment at the LHC.
Abstract: First measurements of the W -> lnu and Z/gamma* -> ll (l = e, mu) production cross sections in proton-proton collisions at sqrt(s) = 7 TeV are presented using data recorded by the ATLAS experiment at the LHC. The results are based on 2250 W -> lnu and 179 Z/gamma* -> ll candidate events selected from a data set corresponding to an integrated luminosity of approximately 320 nb-1. The measured total W and Z/gamma*-boson production cross sections times the respective leptonic branching ratios for the combined electron and muon channels are $\stotW$ * BR(W -> lnu) = 9.96 +- 0.23(stat) +- 0.50(syst) +- 1.10(lumi) nb and $\stotZg$ * BR(Z/gamma* -> ll) = 0.82 +- 0.06(stat) +- 0.05(syst) +- 0.09(lumi) nb (within the invariant mass window 66 < m_ll < 116 GeV). The W/Z cross-section ratio is measured to be 11.7 +- 0.9(stat) +- 0.4(syst). In addition, measurements of the W+ and W- production cross sections and of the lepton charge asymmetry are reported. Theoretical predictions based on NNLO QCD calculations are found to agree with the measurements.
TL;DR: A panel of genes might offer a feasible approach to assessing mesenchymal stromal cell quality with regard to the state of replicative senescence in advance of therapeutic application.
Abstract: Background Research on mesenchymal stromal cells has created high expectations for a variety of therapeutic applications. Extensive propagation to yield enough mesenchymal stromal cells for therapy may result in replicative senescence and thus hamper long-term functionality in vivo . Highly variable proliferation rates of mesenchymal stromal cells in the course of long-term expansions under varying culture conditions may already indicate different propensity for cellular senescence. We hypothesized that senescence-associated regulated genes differ in mesenchymal stromal cells propagated under different culture conditions.
Design and Methods Human bone marrow-derived mesenchymal stromal cells were cultured either by serial passaging or by a two-step protocol in three different growth conditions. Culture media were supplemented with either fetal bovine serum in varying concentrations or pooled human platelet lysate.
Results All mesenchymal stromal cell preparations revealed significant gene expression changes upon long-term culture. Especially genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all mesenchymal stromal cell preparations.
Conclusions Long-term cell growth induced similar gene expression changes in mesenchymal stromal cells independently of isolation and expansion conditions. In advance of therapeutic application, this panel of genes might offer a feasible approach to assessing mesenchymal stromal cell quality with regard to the state of replicative senescence.
TL;DR: In this article, the performance of high-level trigger, identification, and reconstruction algorithms for a broad range of muon momenta was evaluated using a large data sample of cosmic-ray muons recorded in 2008.
Abstract: The performance of muon reconstruction in CMS is evaluated using a large data sample of cosmic-ray muons recorded in 2008. Efficiencies of various high-level trigger, identification, and reconstruction algorithms have been measured for a broad range of muon momenta, and were found to be in good agreement with expectations from Monte Carlo simulation. The relative momentum resolution for muons crossing the barrel part of the detector is better than 1% at 10 GeV/c and is about 8% at 500 GeV/c, the latter being only a factor of two worse than expected with ideal alignment conditions. Muon charge misassignment ranges from less than 0.01% at 10 GeV/c to about 1% at 500 GeV/c.
TL;DR: In this paper, the performance of four global FAPAR datasets (MODIS, CYCLOPES, JRC and GLOBCARBON) over Northern Eurasia in the year 2000 via comparison is presented.
TL;DR: In this article, the SMOSMANIA soil moisture network in Southwestern France is used to evaluate modelled and remotely sensed soil moisture products, and the surface soil moisture (SSM) measured in situ at 5 cm permits to evaluate SSM from the SIM operational hydrometeorological model of Meteo-France and to perform a cross-evaluation of the normalised SSM estimates derived from coarse-resolution (25 km) active microwave observations from the ASCAT scatterometer instrument (C-band, onboard METOP), issued by EUMETSAT and
Abstract: . The SMOSMANIA soil moisture network in Southwestern France is used to evaluate modelled and remotely sensed soil moisture products. The surface soil moisture (SSM) measured in situ at 5 cm permits to evaluate SSM from the SIM operational hydrometeorological model of Meteo-France and to perform a cross-evaluation of the normalised SSM estimates derived from coarse-resolution (25 km) active microwave observations from the ASCAT scatterometer instrument (C-band, onboard METOP), issued by EUMETSAT and resampled to the Discrete Global Grid (DGG, 12.5 km gridspacing) by TU-Wien (Vienna University of Technology) over a two year period (2007–2008). A downscaled ASCAT product at one kilometre scale is evaluated as well, together with operational soil moisture products of two meteorological services, namely the ALADIN numerical weather prediction model (NWP) and the Integrated Forecasting System (IFS) analysis of Meteo-France and ECMWF, respectively. In addition to the operational SSM analysis of ECMWF, a second analysis using a simplified extended Kalman filter and assimilating the ASCAT SSM estimates is tested. The ECMWF SSM estimates correlate better with the in situ observations than the Meteo-France products. This may be due to the higher ability of the multi-layer land surface model used at ECMWF to represent the soil moisture profile. However, the SSM derived from SIM corresponds to a thin soil surface layer and presents good correlations with ASCAT SSM estimates for the very first centimetres of soil. At ECMWF, the use of a new data assimilation technique, which is able to use the ASCAT SSM, improves the SSM and the root-zone soil moisture analyses.
TL;DR: In this article, the operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described and the stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of light monitoring system is presented.
Abstract: The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75 848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented.
TL;DR: In this paper, noise rejection algorithms are applied to LHC collision data at the trigger level or in the offline analysis to remove 90% of noise events with fake missing transverse energy above 100 GeV, which is sufficient for the physics trigger operation.
Abstract: Commissioning studies of the CMS hadron calorimeter have identified sporadic uncharacteristic noise and a small number of malfunctioning calorimeter channels. Algorithms have been developed to identify and address these problems in the data. The methods have been tested on cosmic ray muon data, calorimeter noise data, and single beam data collected with CMS in 2008. The noise rejection algorithms can be applied to LHC collision data at the trigger level or in the offline analysis. The application of the algorithms at the trigger level is shown to remove 90% of noise events with fake missing transverse energy above 100 GeV, which is sufficient for the CMS physics trigger operation.
TL;DR: In this paper, the Pre-print version of the article can be accessed from the link below - Copyright @ 2010 IOP, and the official published version can be found in the link above.
Abstract: This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOP
DOI•
04 Oct 2010
TL;DR: The Eurobarometer 73.1 was used as part of the research project Sensitive Technologies and European Public Ethics (STEPE) as discussed by the authors, which was funded by the Science in Society Programme of the EC's Seventh Framework Programme for Research and Technological Development (FP7).
Abstract: George Gaskell and colleagues designed, analysed and interpreted the Eurobarometer 73.1 on the Life Sciences and Biotechnology as part of the research project Sensitive Technologies and European Public Ethics (STEPE), funded by the Science in Society Programme of the EC’s Seventh Framework Programme for Research and Technological Development (FP7).
T. Aaltonen1, Jahred Adelman2, B. Álvarez González3, B. Álvarez González4 +613 more•Institutions (85)
TL;DR: In this article, the PACS numbers: 13.87.Ce, 14.60.Cd and 14.21 paginas, 15 figuras, 3 tablas.
Abstract: 21 paginas, 15 figuras, 3 tablas.-- PACS numbers: 13.87.Ce, 14.60.Cd, 14.60.-- CDF Collaboration: et al.
TL;DR: In this article, the authors report their experience with endoscopic procedures for arachnoid cyst and report that the most frequent cyst location is the most difficult to treat and a long-term follow-up is recommended since recurrence can occur many years after the procedure.
Abstract: Background Surgical treatment of arachnoid cysts remains under debate. Although many authors favor endoscopic techniques, others attribute a higher recurrence rate to the endoscope. Objective The authors report their experience with endoscopic procedures for arachnoid cyst. Methods All pure endoscopic procedures for arachnoid cysts performed by the authors were analyzed. Particular reference was given to surgical complications and patient outcome in relation to cyst location and endoscopic technique. Results Sixty-six endoscopic procedures were performed in 61 patients (mean age, 28 years; range, 23 days to 74 years; 35 males, 26 females). The main presenting symptoms were cephalgia (61%), hemisymptoms (18%), and macrocephalus (18%). Cyst location was temporobasal (34%), suprasellar (21%), at the cisterna quadrigemina (18%), paraxial supratentorial (16%), and various (10%). Thirty cystocisternostomies, 14 ventriculocystostomies, 12 cystoventriculostomies, and 10 ventriculocystocisternostomies were performed. The overall clinical success rate was 90%. The endoscopic technique was abandoned in 4 cases (7%). Postoperative complications were found in 16%; there was only one permanent deficit (2%). Five recurrences (8%) occurred up to 7 years after the first procedure. Of the various locations, the temporobasal cysts were the most difficult to treat with lowest clinical success (81%), highest recurrence (19%), and highest complication rate (24%). Of the various endoscopic techniques, ventriculocystostomy and ventriculocystocisternostomy reached the highest success rates with 100%. Conclusions Endoscopic techniques provide very good results in arachnoid cyst treatment. The most frequent cyst location is the most difficult to treat. A long-term follow-up is recommended since recurrences can occur many years after the procedure.
TL;DR: It is demonstrated that topical treatment with a TLR-7 agonist, imiquimod, can elicit significant regression of spontaneous breast cancers in neu transgenic mice, a model of human HER-2/neu+ breast cancer, and blocking IL-10 could enhance the therapeutic efficacy of these agents.
Abstract: Multiple TLR agonists have been shown to have antitumor effects in animal models. However, the therapeutic efficacy of TLR agonist monotherapy in cancer treatment has been limited, and the mechanisms of failure remain unknown. We demonstrate that topical treatment with a TLR-7 agonist, imiquimod, can elicit significant regression of spontaneous breast cancers in neu transgenic mice, a model of human HER-2/neu(+) breast cancer. However, tumor growth progressed once imiquimod therapy was ended. Gene expression analysis using tumor-derived RNA demonstrated that imiquimod induced high levels of IL-10 in addition to TNF-alpha and IFN-gamma. Elevated levels of circulating IL-10 were also detected in sera from imiquimod-treated mice. Elevated serum IL-10 appeared to be derived from IL-10 and dual cytokine secreting (IFN-gamma(+) and IL-10(+)) CD4(+) T cells rather than CD4(+)CD25(+)Foxp3(+) T regulatory cells, which were also induced by imiquimod treatment. Blockade of IL-10, but not TGF-beta, enhanced the antitumor effect of imiquimod by significantly prolonging survival in treated mice. These data suggest that the excessive inflammation induced by TLR agonists may result in a self-regulatory immunosuppression via IL-10 induction and that blocking IL-10 could enhance the therapeutic efficacy of these agents.
TL;DR: Results indicate that N-cadherin is involved in the bidirectional interaction of human HPC with their cellular determinants in the niche.
T. Aaltonen1, Jahred Adelman2, B. Álvarez González3, B. Álvarez González4 +613 more•Institutions (86)
TL;DR: In this paper, a CDF measurement of the total cross section and rapidity distribution, d σ / d y, for γ ∗ / Z → e + e − events in the Z boson mass region ( 66 M e e 116 GeV / c 2 ) produced in p p ¯ collisions at s = 1.96 TeV with 2.1 fb − 1 of integrated luminosity.
TL;DR: The Cosmic Run At Four Tesla (CMS) data-taking exercise was conducted by the CMS Collaboration in late 2008 to complete the commissioning of the experiment for extended operation.
Abstract: The CMS Collaboration conducted a month-long data-taking exercise known as the Cosmic Run At Four Tesla in late 2008 in order to complete the commissioning of the experiment for extended operation. The operational lessons resulting from this exercise were addressed in the subsequent shutdown to better prepare CMS for LHC beams in 2009. The cosmic data collected have been invaluable to study the performance of the detectors, to commission the alignment and calibration techniques, and to make several cosmic ray measurements. The experimental setup, conditions, and principal achievements from this data-taking exercise are described along with a review of the preceding integration activities.
TL;DR: In this paper, the Level-1 trigger was used to select cosmic ray muons and LHC beam events during data-taking runs in 2008, and to estimate the level of detector noise.
Abstract: The CMS Level-1 trigger was used to select cosmic ray muons and LHC beam events during data-taking runs in 2008, and to estimate the level of detector noise. This paper describes the trigger components used, the algorithms that were executed, and the trigger synchronisation. Using data from extended cosmic ray runs, the muon, electron/photon, and jet triggers have been validated, and their performance evaluated. Efficiencies were found to be high, resolutions were found to be good, and rates as expected.