julilili42/papers huggingface dataset:
Comparison of [68Ga]DOTATOC-PET/CT and whole-body MRI in staging of neuroendocrine tumors
2011-01-01

126 Objectives To compare the diagnostic performance of 68Ga-DOTATOC-PET/CT and whole-body (wb) MRI for staging of neuroendocrine tumors (NET). Methods In 51 patients (25 f, 26 m, mean 57 yrs) with histologically proven NET and suspicion of metastatic spread 68Ga-DOTATOC-PET/CT and wbMRI were performed within Results 41 of 51 (80%) NET patients had 593 metastatic lesions (lung: 54, liver: 266, bone: 131, lymph node (LN): 99, other: 43). 68Ga-DOTATOC-PET was false negative in 5/41 (12%) of patients due to lack of SSTR expression. Of all 593 detected lesions, PET identified 370 (62%) true positive lesions, CT 482 (81%), PET/CT 545 (92%) and wbMRI 54 (91%). Comparison of organ-based detection rates between PET/CT and wbMRI revealed significantly higher sensitivity of PET/CT in detecting metastatic LN (100% vs 73%; p Conclusions PET/CT and wbMRI showed comparable overall detection rates for metastatic involvement in NET but significantly differed in organ-based detection rates with superiority of PET/CT for LN and pulmonary lesions and of wbMRI for liver and bone metastases
The Alg5 ortholog Wollknäuel is essential for correct epidermal differentiation during Drosophila late embryogenesis
2011-01-02

The formation of an extracellular matrix (ECM) presupposes an ordered delivery of its components to ensure its stereotypic architecture. The Drosophila cuticle is an ECM produced by the epidermis at its apical site and is characterized by a layered organization. To understand the mechanisms of cuticle assembly during development, we have investigated early aspects of protein N-glycosylation, i.e. the attachment of a dolichol-linked oligosaccharide to distinct Asn sites of a protein known to be essential for sorting in the secretory pathway. Mutations in the Drosophila alg5 gene wollknäuel (wol) that codes for an enzyme initiating the glucosylation of the dolichol-linked oligosaccharide decrease, as expected, glucosylation and the amounts of N-glycosylated proteins such as the cuticle-organizing factor Knickkopf, without affecting their correct localization. At the same time, the polarity determinants Crumbs and atypical protein kinase C accumulate at the apical plasma membrane in wol deficient embryos. In part, these perturbations may also be caused by the unfolded protein response, which is commonly triggered by ER stress and downsizes transcription and translation in general. In any case, they are associated with the loss of cuticle layering and aberrant apical plasma membrane organization suggesting that glucosylation, either directly or indirectly through controlling protein degradation, is important for the efficient and balanced deployment of the biochemical functions of secreted and membrane-associated proteins during epidermal differentiation.
The Mineralogical Diversity of Alkaline Igneous Rocks: Critical Factors for the Transition from Miaskitic to Agpaitic Phase Assemblages
2011-01-03

Geochemically, the large family of alkaline plutonic rocks (both Qtz-undersaturated and -oversaturated compositions) can be subdivided into metaluminous [(Na2O + K2O) < Al2O3] and peralkaline [(Na2O + K2O) > Al2O3] types. In this paper, we discuss two important aspects of the mineralogical evolution of such rocks. With respect to their Fe–Mg phases, a major mineralogical transition observed is the precipitation of arfvedsonite or aegirine instead of fayalite or magnetite (± ilmenite). The relative stability of these phases is controlled by oxygen fugacity and Na activity in the crystallizing melts. If Na activity in the melt is high enough, arfvedsonite + aegirine form a common assemblage in peralkaline rocks under both reduced and oxidized conditions. Major mineralogical differences within this rock group exist with respect to their high field strength element (HFSE)-rich minerals: most syenitic rocks, known as miaskites, contain zircon, titanite or ilmenite as HFSE-rich minerals, whereas in agpaites complex Na–K–Ca–(Ti, Zr) silicates incorporate the HFSE. Similarly, only a small group of peralkaline granites are found to lack zircon, titanite or ilmenite but instead contain Na–K–Ca–(Ti, Zr) silicates. Here, we present a detailed phase petrological analysis of the chemical parameters (μNa2O, μCaO, μK2O) that influence the transition from miaskitic to agpaitic rocks. Based on the occurrence of Ti and Zr minerals, several transitional mineral assemblages are identified and two major evolution trends for agpaites are distinguished: a high-Ca trend, which is exemplified by the alkaline rocks of the Kola Province, Russia, and a Ca-depletion trend, which is displayed by the alkaline rocks of the Gardar Province, South Greenland. Both trends show significant Na-enrichment during magmatic evolution. High-Ca agpaites evolve from nephelinitic parental melts that did not crystallize large amounts of plagioclase. In contrast, agpaites showing Ca-depletion originate by extensive fractionation of plagioclase from basaltic parental melts. In some peralkaline granites evolutionary trends are observed that culminate in agpaite-like HFSE-mineral associations in the most evolved rocks.
Arabidopsis SNARE protein SEC22 is essential for gametophyte development and maintenance of Golgi‐stack integrity
2011-01-03

Summary Membrane traffic contributes to plant growth and development. However, the functional significance of SNARE proteins involved in membrane fusion of the early secretory pathway has not been explored with respect to plant development. Here we analyze the Arabidopsis v‐SNARE SEC22. Loss of SEC22 function impairs gametophyte development, as indicated by reciprocal crosses between wild‐type plants and plants heterozygous for T‐DNA insertions in the SEC22 gene. sec22 mutant pollen becomes abnormal during the bicellular stage, eventually giving rise to degenerated pollen grains. Most mutant embryo sacs fail to support embryogenesis and display unfused polar nuclei in their central cell. Immunolocalization by both light and electron microscopy revealed an association of mutant‐complementing Myc‐tagged SEC22 with the central and peripheral endoplasmic reticulum (ER). Ultrastructural analysis of developing sec22 mutant pollen demonstrated Golgi fragmentation and consumption. As a consequence, the plasma membrane‐targeted syntaxin SYP124 was retained in the ER. Our results suggest that SEC22 plays an essential role in early secretory traffic between the ER and the Golgi.
The Influence on Cell Growth Properties in Different Microtiterplate Types by Corona‐Dielectric Barrier Discharge Plasma at Atmospheric Pressure
2011-01-03

Abstract In high throughput processes with living cells maintenance of sterility is a cost‐intensive but essential requirement. In the course of this work an atmospheric plasma process was developed for the sterilization of microtiterplates in such assays. In a next step it was necessary to investigate, if this plasma treatment changes surface properties for cell growth of different microtiterplate types. The results showed that this kind of plasma treatment did not significantly alter growth characteristics of different cell types in microtiterplates which were tissue culture treated or coated with collagen I or poly‐D‐lysine. Furthermore, these results revealed no detrimental effects of the applied corona‐dielectric barrier discharge (corona‐DBD) procedure on the tested surfaces and is therefore suitable for the sterilization of microtiterplates in automated cellular assays. magnified image
Nucleosome‐induced neutrophil activation occurs independently of TLR9 and endosomal acidification: Implications for systemic lupus erythematosus
2011-01-04

Abstract The nucleosome is a major autoantigen known to activate PMN in systemic lupus erythematosus (SLE). TLR9 recognizes bacterial and even mammalian DNA under certain circumstances. Nevertheless, the role of TLR9 in SLE development is still unclear. Since nucleosomes are composed of DNA, we investigated whether TLR9 is required for nucleosome‐induced PMN activation. Isolated neutrophils were cultured with nucleosomes, plasma from lupus patients and other stimuli in the presence/absence of various inhibitors. Cells were analyzed by flow cytometry, ELISA and confocal microscopy. We found that nucleosomes circulating in lupus plasma induce the secretion of pro‐inflammatory cytokines by PMN. Nucleosomes activate human PMN independently of unmethylated CpG sequences in nucleosomal DNA, leading to IL‐8/IL‐6/TNF secretion and CD11b up‐regulation. Nucleosomes accumulate in the cytoplasm of PMN upon endocytosis, induce TLR9 up‐regulation and act synergistically with TLR9 ligands. Nucleosome‐induced activation was not inhibited by polymyxin B (PB), chloroquine (CQ), ammonium chloride (AC) or a TLR9 antagonist. Moreover, both PMN isolated from WT and TLR9‐KO mice were activated by nucleosomes, as detected by MIP‐2 secretion and CD11b up‐regulation. Activation occurred therefore independently of endotoxins, endosomal acidification, TLR9 and CpG motifs. TLR9 may thus be differently required in the triggering of nucleosome‐induced innate immunity and anti‐nucleosome B‐cell autoimmunity.
Resonant Raman spectra of diindenoperylene thin films
2011-01-04

Resonant and preresonant Raman spectra obtained on diindenoperylene (DIP) thin films are interpreted with calculations of the deformation of a relaxed excited molecule with density functional theory (DFT). The comparison of excited state geometries based on time-dependent DFT or on a constrained DFT scheme with observed absorption spectra of dissolved DIP reveals that the deformation pattern deduced from constrained DFT is more reliable. Most observed Raman peaks can be assigned to calculated \\documentclass[12pt]{minimal}\\begin{document} \\end{document}Ag-symmetric breathing modes of DIP or their combinations. As the position of one of the laser lines used falls into a highly structured absorption band, we have carefully analyzed the Raman excitation profile arising from the frequency dependence of the dielectric tensor. This procedure gives Raman cross sections in good agreement with the observed relative intensities, both in the fully resonant and in the preresonant case.
Novel Regulation of Parkin Function through c-Abl-Mediated Tyrosine Phosphorylation: Implications for Parkinson's Disease
2011-01-05

Mutations in parkin , an E3 ubiquitin ligase, are the most common cause of autosomal-recessive Parkinson's disease (PD). Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl links parkin to sporadic forms of PD via tyrosine phosphorylation. Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in striatum of adult C57BL/6 mice. Activated c-Abl was found in the striatum of PD patients. Concomitantly, parkin was tyrosine-phosphorylated, causing loss of its ubiquitin ligase and cytoprotective activities, and the accumulation of parkin substrates, AIMP2 (aminoacyl tRNA synthetase complex-interacting multifunctional protein 2) (p38/JTV-1) and FBP-1.STI-571, a selective c-Abl inhibitor, prevented tyrosine phosphorylation of parkin and restored its E3 ligase activity and cytoprotective function both in vitro and in vivo . Our results suggest that tyrosine phosphorylation of parkin by c-Abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic PD. Moreover, inhibition of c-Abl offers new therapeutic opportunities for blocking PD progression.
On using intelligent computer-assisted language learning in real-life foreign language teaching and learning
2011-01-05

Abstract This paper explores the motivation and prerequisites for successful integration of Intelligent Computer-Assisted Language Learning (ICALL) tools into current foreign language teaching and learning (FLTL) practice. We focus on two aspects, which we argue to be important for effective ICALL system development and use: (i) the relationship between activity design and restrictions needed to make natural language processing tractable and reliable, and (ii) pedagogical considerations and the influence of activity design choices on the integration of ICALL systems into FLTL practice.
Prognostic Importance of Histone MethyltransferaseMLL5Expression in Acute Myeloid Leukemia
2011-01-05

Purpose To assess the prognostic importance of mixed lineage leukemia 5 (MLL5) expression in acute myeloid leukemia (AML). Patients and Methods MLL5 transcript levels from 509 patients with AML who were treated in multicenter trials AML SHG 0199 and AML SHG 0295 and 48 healthy volunteers were analyzed by real-time reverse-transcription polymerase chain reaction in the context of other molecular markers (NPM1, FLT3, CEBPA, IDH1/IDH2, NRAS, KIT, MN1, BAALC, ERG, and WT1). Results Patients with high (n = 127) compared with low (n = 382) MLL5 expression had a higher complete response rate in multivariate analysis (odds ratio, 1.87; 95% CI, 1.08 to 3.24; P = .026). In multivariate analysis, high MLL5 expression was a favorable prognostic marker for overall survival (OS; hazard ratio [HR], 0.66; 95% CI, 0.49 to 0.89; P = .007) and relapse-free survival (RFS; HR, 0.72; 95% CI, 0.52 to 1.01; P = .057). Patient characteristics, cytogenetic aberrations, and gene mutations were similarly distributed between patients with high and low MLL5 expression except for a higher platelet count in those with high MLL5 expression. MLL5 expression independently predicted prognosis in cytogenetically normal AML patients (n = 268; OS: HR, 0.53; 95% CI, 0.33 to 086; P = .011; RFS: HR, 0.61; 95% CI, 0.38 to 0.99; P = .05) and in patients with core-binding factor leukemias (n = 81; OS: HR, 0.12; 95% CI, 0.02 to 0.91; P = .04; RFS: HR, 0.18; 95% CI, 0.04 to 0.77; P = .02). The prognostic importance of high MLL5 expression was independently validated in 167 patients treated in the AMLSG 07/04 trial (OS: HR, 0.5; 95% CI, 0.27 to 0.92; P = .023; RFS: HR, 0.49; 95% CI, 0.25 to 0.96; P = .033). Conclusion High MLL5 expression levels are associated with a favorable outcome and may improve risk and treatment stratification in AML.
Large-Scale Learning of Structure−Activity Relationships Using a Linear Support Vector Machine and Problem-Specific Metrics
2011-01-05

The goal of this study was to adapt a recently proposed linear large-scale support vector machine to large-scale binary cheminformatics classification problems and to assess its performance on various benchmarks using virtual screening performance measures. We extended the large-scale linear support vector machine library LIBLINEAR with state-of-the-art virtual high-throughput screening metrics to train classifiers on whole large and unbalanced data sets. The formulation of this linear support machine has an excellent performance if applied to high-dimensional sparse feature vectors. An additional advantage is the average linear complexity in the number of non-zero features of a prediction. Nevertheless, the approach assumes that a problem is linearly separable. Therefore, we conducted an extensive benchmarking to evaluate the performance on large-scale problems up to a size of 175000 samples. To examine the virtual screening performance, we determined the chemotype clusters using Feature Trees and integrated this information to compute weighted AUC-based performance measures and a leave-cluster-out cross-validation. We also considered the BEDROC score, a metric that was suggested to tackle the early enrichment problem. The performance on each problem was evaluated by a nested cross-validation and a nested leave-cluster-out cross-validation. We compared LIBLINEAR against a Naïve Bayes classifier, a random decision forest classifier, and a maximum similarity ranking approach. These reference approaches were outperformed in a direct comparison by LIBLINEAR. A comparison to literature results showed that the LIBLINEAR performance is competitive but without achieving results as good as the top-ranked nonlinear machines on these benchmarks. However, considering the overall convincing performance and computation time of the large-scale support vector machine, the approach provides an excellent alternative to established large-scale classification approaches.
Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study
2011-01-06

Quantitative variables derived from CSF dynamics allow differentiation between clinically overlapping entities such as shunt-responsive normal pressure hydrocephalus and brain atrophy (not shunt responsive) as well as allowing the detection of shunt malfunction (partial or complete blockage) or overdrainage. This observational study is intended to serve as an update for our understanding of quantitative testing of CSF dynamics.
On the dynamics and collisional growth of planetesimals in misaligned binary systems
2011-01-06

Context. Abridged. Many stars are members of binary systems. During early phases when the stars are surrounded by discs, the binary orbit and disc midplane may be mutually inclined. The discs around T Tauri stars will become mildly warped and undergo solid body precession around the angular momentum vector of the binary system. It is unclear how planetesimals in such a disc will evolve and affect planet formation. Aims. We investigate the dynamics of planetesimals embedded in discs that are perturbed by a binary companion on a circular, inclined orbit. We examine collisional velocities of the planetesimals to determine when they can grow through accretion. We vary the binary inclination, binary separation, D, disc mass, and planetesimal radius. Our standard model has D=60 AU, inclination=45 deg, and a disc mass equivalent to the MMSN. Methods. We use a 3D hydrodynamics code to model the disc. Planetesimals are test particles which experience gas drag, the gravitational force of the disc, the companion star gravity. Planetesimal orbit crossing events are detected and used to estimate collisional velocities. Results. For binary systems with modest inclination (25 deg), disc gravity prevents planetesimal orbits from undergoing strong differential nodal precession (which occurs in absence of the disc), and forces planetesimals to precess with the disc on average. For bodies of different size the orbit planes become modestly mutually inclined, leading to collisional velocities that inhibit growth. For larger inclinations (45 degrees), the Kozai effect operates, leading to destructively large relative velocities. Conclusions. Planet formation via planetesimal accretion is difficult in an inclined binary system with parameters similar to those considered in this paper. For systems in which the Kozai mechanism operates, the prospects for forming planets are very remote.
Autophagy in protists
2011-01-07

Autophagy is the degradative process by which eukaryotic cells digest their own components using acid hydrolases within the lysosome. Originally thought to function almost exclusively in providing starving cells with nutrients taken from their own cellular constituents, autophagy is in fact involved in numerous cellular events including differentiation, turnover of macromolecules and organelles, and defense against parasitic invaders. During the last 10-20 years, molecular components of the autophagic machinery have been discovered, revealing a complex interactome of proteins and lipids, which, in a concerted way, induce membrane formation to engulf cellular material and target it for lysosomal degradation. Here, our emphasis is autophagy in protists. We discuss experimental and genomic data indicating that the canonical autophagy machinery characterized in animals and fungi appeared prior to the radiation of major eukaryotic lineages. Moreover, we describe how comparative bioinformatics revealed that this canonical machinery has been subject to moderation, outright loss or elaboration on multiple occasions in protist lineages, most probably as a consequence of diverse lifestyle adaptations. We also review experimental studies illustrating how several pathogenic protists either utilize autophagy mechanisms or manipulate host-cell autophagy in order to establish or maintain infection within a host. The essentiality of autophagy for the pathogenicity of many parasites, and the unique features of some of the autophagy-related proteins involved, suggest possible new targets for drug discovery. Further studies of the molecular details of autophagy in protists will undoubtedly enhance our understanding of the diversity and complexity of this cellular phenomenon and the opportunities it offers as a drug target.
Hepatitis C Virus Impairs the Induction of Cytoprotective Nrf2 Target Genes by Delocalization of Small Maf Proteins
2011-01-08

The expression of a variety of cytoprotective genes is regulated by short cis-acting elements in their promoters, called antioxidant response elements (AREs). A central regulator of ARE-mediated gene expression is the NF-E2-related factor 2 (Nrf2). Nrf2/ARE-regulated genes are crucial for the maintenance of cellular integrity. Hepatitis C virus inhibits the induction of ARE-regulated genes, but neither induction nor inhibition of ARE-regulated gene expression affects HCV replication directly. In HCV-replicating cells the core protein triggers the delocalization of sMaf proteins from the nucleus to the replicon complex. Here sMafs bind to NS3. The extranuclear sMaf proteins prevent Nrf2 from entry in the nucleus and thereby inhibit the induction of Nrf2/ARE-regulated genes. This results in the decreased expression of cytoprotective genes. Consistent with this finding, the elimination of ROI is impaired in HCV-replicating cells as demonstrated by elevated protein oxidation or 8-OH-dG formation, reflecting DNA damage. In conclusion, these data identified a novel mechanism of Nrf2 regulation and suggest that the HCV-dependent inhibition of Nrf2/ARE-regulated genes confers to the HCV-associated pathogenesis by elevation of intracellular ROI that affect integrity of the host genome and regenerative processes.
Rootless with undetectable meristem 1 encodes a monocot‐specific AUX/IAA protein that controls embryonic seminal and post‐embryonic lateral root initiation in maize
2011-01-10

Summary The maize ( Zea mays L.) rum1‐R ( rootless with undetectable meristems 1‐Reference ) mutant does not initiate embryonic seminal roots and post‐embryonic lateral roots at the primary root. Map‐based cloning revealed that Rum1 encodes a 269 amino acid (aa) monocot‐specific Aux/IAA protein. The rum1‐R protein lacks 26 amino acids including the GWPPV degron sequence in domain II and part of the bipartite NLS (nuclear localization sequence). Significantly reduced lateral root density (approximately 35%) in heterozygous plants suggests that the rum1‐R is a semi‐dominant mutant. Overexpression of rum1‐R under the control of the maize MSY ( M ethionine SY nthase) promoter supports this notion by displaying a reduced number of lateral roots (31–37%). Functional characterization suggests that Rum1 is auxin‐inducible and encodes a protein that localizes to the nucleus. Moreover, RUM1 is unstable with a half life time of approximately 22 min while the mutant rum1‐R protein is very stable. In vitro and in vivo experiments demonstrated an interaction of RUM1 with ZmARF25 and ZmARF34 ( Z. mays AUXIN RESPONSE FACTOR 25 and 34). In summary, the presented data suggest that Rum1 encodes a canonical Aux/IAA protein that is required for the initiation of embryonic seminal and post‐embryonic lateral root initiation in primary roots of maize.
jCompoundMapper: An open source Java library and command-line tool for chemical fingerprints
2011-01-10

jCompoundMapper is a library for chemical graph fingerprints with several tweaking possibilities and exporting options for open source data mining toolkits. The quality of the data mining results, the conversion speed, the LPGL software license, the command-line interface, and the exporters should be useful for many applications in cheminformatics like benchmarks against literature methods, comparison of data mining algorithms, similarity searching, and similarity-based data mining.