julilili42/papers huggingface dataset:
Timing accuracy and capabilities of XMM-Newton
2004-02-03

Since December 1999, ESA's large X-ray space observatory XMM-Newton operates in a highly eccentric 48-h orbit which allows for long uninterrupted exposure times. The three payload instruments EPIC, RGS, and OM yield scientific data of high quality and sensitivity. We report here on the current timing capabilities of all three instruments by showing results from analyses on relative and absolute timing. In this context we discuss the process of correlating local onboard event arrival times to terrestrial time frames and present some detailed results from time correlation analyses. This involves investigations on the performance of the onboard quartz oscillator that have been performed. In addition we describe problematic timing data anomalies in the EPIC-pn data and their treatment by the SAS. We show recent examples of timing analyses.
EPIC pn-CCD detector aboard XMM-Newton: status of the background calibration
2004-02-03

We report on the current status of the background calibration of the EPIC pn-CCD camera on board XMM-Newton. The intrinsic background is comprised of internal electronic noise, and continuous and fluorescent X-ray emission induced by high-energy particles. Soft protons passing through the X-ray telescope (and finally also true cosmic X-rays) contribute to the registered events. The camera background has been monitored by using data in closed filter positions for three years; we review the spectral, spatial, and temporal distribution, for all commissioned instrument modes. This paper also discusses briefly the effects on scientific data analysis and conclusions for further observations and detectors.
M-cadherin transcription in satellite cells from normal and denervated muscle
2004-02-03

Satellite cells (SC) in adult muscle are quiescent in the G 0 phase of the cell cycle. In the present study we determined whether SC after denervation upregulate M-cadherin, an adhesion molecule that is upregulated with differentiation and fusion. We also monitored primary cultures of SC from denervated muscle for expression of the transcription factors of the MyoD family to determine whether SC from denervated muscle can be activated in vitro. Hindlimb muscles of rats were denervated under anesthesia, and rats were killed after 2-28 days. The SC of the denervated limbs were pooled and either assessed for M-cadherin mRNA by using real-time RT-PCR or cultured in vitro. The cultures were processed for RT-PCR or immunofluorescence for expression of the transcription factors of the MyoD family. Hindlimb muscles of M-cadherin knockout mice were denervated under anesthesia, mice were killed after 2-28 days, and cells were stained for β-galactosidase activity by X-gal histochemistry. In vitro, primary SC cultures from rat muscle denervated for 2-28 days expressed transcripts of myf5, MyoD, myogenin, and MRF4 as SC from normal innervated muscle. In vivo, M-cadherin transcription was not upregulated in SC from denervated rat muscle when compared with normal muscle. Moreover, β-galactosidase activity was not detected in denervated mouse muscle. The finding that SC do not upregulate M-cadherin after denervation supports the notion that they remain in the G 0 phase of the cell cycle in vivo. However, the cells retain the capacity to pass through the proliferative and differentiative program when robustly stimulated to do so in vitro.
Effect of soft flares on XMM-Newton EPIC-pn timing mode data
2004-02-03

The EPIC-pn CCD Camera on board the ESA X-ray observatory XMM-Newton is a very sensitive and versatile instrument with many observing modes. One of the modes, the timing mode, was designed so that a time resolution of 0.029 milliseconds can be achieved. This mode is important for observing bright variable sources with a very high time resolution. Up to now it has only been possible to use the spectra down to 300-400 eV in this mode. Below this energy the data appears to be affected by soft flares which are caused by stack overflows generated by high energy particles. We present a method that can be used to mitigate the effect these flares have on the data and discuss the improvement that this brings to the timing mode spectra. This new method will at last make it possible to get spectra down to the lowest energies detectable in this mode. This is particularly interesting for timing studies of isolated neutron stars and other variable objects, such as magnetic CVs, with very soft spectra.
Fast timing on XEUS
2004-02-03

Fast X-ray timing observations are a method to probe strong gravity fields around compact massive objects. The European X-ray Evolving Universe Spectroscopy (XEUS) mission with its large collecting area telescope will be able to deliver the required extremely good photon statistics for these studies. The fast timing detector in the focal plane must be able to operate at up to 10<sup>7</sup> incoming photons from the brightest X-ray objects in the sky with an energy resolution of 200 eV FWHM at 5.9 keV at a dead time not exceeding 1% and a time resolution of 10 &mu;sec. Silicon Drift Detectors (SDDs) with their extremely small value of the readout capacitance have proved that they can handle high count rates with simultaneous good energy resolution. For the XEUS fast timing detector it is proposed to operate a multi-channel SDD at an out of focus position to distribute the flux of photons over a number of detector cells.
Iron accumulation, iron‐mediated toxicity and altered levels of ferritin and transferrin receptor in cultured astrocytes during incubation with ferric ammonium citrate
2004-02-04

Abstract The cellular uptake and storage of iron have to be tightly regulated in order to provide iron for essential cellular functions while preventing the iron‐catalysed generation of reactive oxygen species (ROS). In contrast to cells in other organs, little is known about the regulation of iron metabolism in brain cells, particularly in astrocytes. To investigate the regulation of iron metabolism in astrocytes we have used primary astrocyte cultures from the brains of newborn rats. After application of ferric ammonium citrate (FAC), cultured astrocytes accumulated iron in a time‐ (0–48 h) and concentration‐dependent (0.01–1 m m ) manner. This accumulation was prevented if FAC was applied in combination with the iron‐chelator deferoxamine (DFX). Application of FAC to astrocyte cultures caused a strong increase in the cellular content of the iron storage protein ferritin and a decrease in the amount of transferrin receptor (TfR), which is involved in the transferrin‐mediated uptake of iron into cells. In contrast, application of DFX strongly increased the level of TfR. Both up‐regulation of ferritin content by iron application and up‐regulation of TfR content by DFX were prevented by the protein synthesis inhibitor cycloheximide (CHX). During incubation of astrocytes with FAC, a mild and transient increase in the extracellular activity of the cytosolic enzyme lactate dehydrogenase and in the concentration of intracellular ROS was observed. In contrast, prevention of protein synthesis by CHX during incubation with FAC resulted in significantly more cell loss and a persistent and intense increase in the production of intracellular ROS. These results demonstrate that both iron accumulation and deprivation modulate the synthesis of ferritin and TfR in astrocytes and that protein synthesis is required to prevent iron‐mediated toxicity in astrocytes.
Antioxidant intervention does not affect the response of plasma erythropoietin to short-term normobaric hypoxia in humans
2004-02-06

Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac-α-tocopherol (800 mg/day for 3 wk) and α-lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum α-tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary Po 2 declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.
Quantification of quaternary mixtures of alcohols: a comparison of reflectometric interference spectroscopy and surface plasmon resonance spectroscopy
2004-02-09

In this paper the quantification of quaternary mixtures of the homologous series of the alcohols methanol to n-butanol in the gaseous phase is presented. Time-resolved reflectometric interference spectroscopy (RIfS) and surface plasmon resonance spectroscopy (SPR) are used. An array consisting of two layers of a size-selective microporous polymer (Makrolon®) plus the polar polymer polyetherurethan (PUT) is used for RIfS measurements. The time-dependent kinetics of sorption and desorption of the analytes is evaluated by the use of neural networks. As the time-dependent sensor signals differ significantly for each analyte, quantifications with only a single microporous layer are possible. Thus, measurements using a thinner microporous layer for the SPR set-up are also performed, showing faster sorption and desorption. Therefore, measurements can be performed much faster by using the SPR set-up.
ParSeq: searching motifs with structural and biochemical properties
2004-02-12

Abstract Summary: Searches for variable motifs such as protein-binding sites or promoter regions are more complex than the search for casual motifs. For example, in amino acid sequences comparing motifs alone mostly proves to be insufficient to detect regions that represent proteins with a special function, because the function depends on biochemical properties of individual amino acids (such as polarity or hydrophobicity). Pure string matching programs are not able to find these motifs; hence, we developed ParSeq, a program that combines the search for motifs with certain structural properties, the verification of biochemical properties, an approximate search mechanism and a stepwise creation of the motif description by allowing to search on previously obtained results. Availability: http://www-pr.informatik.uni-tuebingen.de/parseq
Microcontact Printing of DNA Molecules
2004-02-13

The controlled placement of DNA molecules onto solid surfaces is the first step in the fabrication of DNA arrays. The sequential deposition of tiny drops containing the probe DNA fragments using arrays of spotting needles or ink jet nozzles has become a standard. However, a caveat of liquid spotting is the drying of the deposited drop because this creates the typical inhomogeneities, i.e., rims around the spot. Another drawback is that each DNA array is an original and has to be fabricated individually. Microcontact printing is a versatile technique to place proteins onto different target surfaces in uniformly patterned monolayers with high lateral resolution. Here, we show for the first time that DNA can also be printed with equally high resolution in the submicrometer range using an elastomeric stamp with chemically tailored surface. Two regimes for the transfer of the molecules were observed. Finally, microcontact printing of an array of DNA probes onto a solid support and its use in a subsequent hybridization assay was demonstrated.
Feature Selection for Descriptor Based Classification Models. 2. Human Intestinal Absorption (HIA)
2004-02-13

We show that the topological polar surface area (TPSA) descriptor and the radial distribution function (RDF) applied to electronic and steric atom properties, like the conjugated electrotopological state (CETS), are the most relevant features/descriptors for predicting the human intestinal absorption (HIA) out of a large set of 2934 features/descriptors. A HIA data set with 196 molecules with measured HIA values and 2934 features/descriptors were calculated using JOELib and MOE. We used an adaptive boosting algorithm to solve the binary classification problem (AdaBoost.M1) and Genetic Algorithms based on Shannon Entropy Cliques (GA-SEC) variants as hybrid feature selection algorithms. The selection of relevant features was applied with respect to the generalization ability of the classification model, avoiding a high variance for unseen molecules (overfitting).
Feature Selection for Descriptor Based Classification Models. 1. Theory and GA-SEC Algorithm
2004-02-13

The paper describes different aspects of classification models based on molecular data sets with the focus on feature selection methods. Especially model quality and avoiding a high variance on unseen data (overfitting) will be discussed with respect to the feature selection problem. We present several standard approaches and modifications of our Genetic Algorithm based on the Shannon Entropy Cliques (GA-SEC) algorithm and the extension for classification problems using boosting.
Human B lymphoblastoid cells contain distinct patterns of cathepsin activity in endocytic compartments and regulate MHC class II transport in a cathepsin S-independent manner
2004-02-13

Abstract Endocytic proteolysis represents a major functional component of the major histocompatibility complex class II antigen-presentation machinery. Although transport and assembly of class II molecules in the endocytic compartment are well characterized, we lack information about the pattern of endocytic protease activity along this pathway. Here, we used chemical tools that visualize endocytic proteases in an activity-dependent manner in combination with subcellular fractionation to dissect the subcellular distribution of the major cathepsins (Cat) CatS, CatB, CatH, CatD, CatC, and CatZ as well as the asparagine-specific endoprotease (AEP) in human B-lymphoblastoid cells (BLC). Endocytic proteases were distributed in two distinct patterns: CatB and CatZ were most prominent in early and late endosomes but absent from lysosomes, and CatH, CatS, CatD, CatC, and AEP distributed between late endosomes and lysosomes, suggesting that CatB and CatZ might be involved in the initial proteolytic attack on a given antigen. The entire spectrum of protease activity colocalized with human leukocyte antigen-DM and the C-terminal and N-terminal processing of invariant chain (Ii) in late endosomes. CatS was active in all endocytic compartments. Surprisingly and in contrast with results from dendritic cells, inhibition of CatS activity by leucine–homophenylalanine–vinylsulfone-phenol prevented N-terminal processing of Ii but did not alter the subcellular trafficking or surface delivery of class II complexes, as deferred from pulse-chase analysis in combination with subcellular fractionation and biotinylation of cell-surface protein. Thus, BLC contain distinct activity patterns of proteases in endocytic compartments and regulate the intracellular transport and surface-delivery of class II in a CatS-independent manner.
Peptide-Mediated Inhibition of Neutrophil Transmigration by Blocking CD47 Interactions with Signal Regulatory Protein α
2004-02-15

Abstract CD47, a cell surface transmembrane Ig superfamily member, is an extracellular ligand for signal regulatory protein (SIRPα). Interactions between CD47 and SIRPα regulate many important immune cell functions including neutrophil (PMN) transmigration. Here we report identification of a novel function-blocking peptide, CERVIGTGWVRC, that structurally mimics an epitope on CD47 and binds to SIRPα. The CERVIGTGWVRC sequence was identified by panning phage display libraries on the inhibitory CD47 mAb, C5D5. In vitro PMN migration assays demonstrated that peptide CERVIGTGWVRC specifically inhibited PMN migration across intestinal epithelial monolayers and matrix in a dose-dependent fashion. Further studies using recombinant proteins indicated that the peptide specifically blocks CD47 and SIRPα binding in a dose-dependent fashion. Protein binding assays using SIRPα domain-specific recombinant proteins demonstrated that this peptide directly bound to the distal-most Ig loop of SIRPα, the same loop where CD47 binds. In summary, these findings support the relevance of CD47-SIRPα interactions in regulation of PMN transmigration and provide structural data predicting the key residues involved on the surface of CD47. Such peptide reagents may be useful for studies on experimental models of inflammation and provide a template for the design of anti-inflammatory agents.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells
2004-02-15

Abstract Purpose: Overexpression of antiapoptotic Bcl-2 family members has recently been related to resistance to chemo/radiotherapy in several human malignancies, particularly lymphomas. Hence, innovative approaches bypassing this resistance mechanism are required in the therapeutic approach. This study evaluated whether chemoresistance associated with Bcl-2 and Bcl-xL overexpression would be overcome by activating the death receptor pathway by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the Jurkat cell model Experimental Design: We made use of genetically modified Jurkat cells to evaluate the effect of Bcl-2 or Bcl-xL overexpression on the cytotoxic effect produced by the anticancer drugs doxorubicin, etoposide, and oxaliplatin and TRAIL. Caspase activation was detected by cleavage of caspase-8 and -3. The mitochondrial transmambrane potential was assessed by staining with DiOC6 and flow cytometry. Caspase activity was blocked by the broad-spectrum caspase inhibitor zVAD-fmk. Results: Bcl-2 and Bcl-xL overexpression but not lack of caspase-8 protects the Jurkat cells from the anticancer drug-induced cytolysis. However, Bcl-2/Bcl-xL Jurkat cells retained some susceptibility to TRAIL-induced cytolysis. A highly synergistic cytotoxic effect of the combination of TRAIL with any of the antiblastic used in this study was detected in the chemoresistant cells. This effect was associated with mitochondrial disassemblage and dependent on caspase activation Conclusions: The combination of TRAIL with conventional anticancer drugs may prove to be useful in the treatment of antiapoptotic Bcl-2 family proteins-expressing malignancies.
Chronological aging leads to apoptosis in yeast
2004-02-16

During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone.
The Control of the Nitrogen Inversion in Alkyl‐Substituted Diaziridines
2004-02-16

Abstract For the first time the nitrogen inversion barriers in 3,3‐unsubstituted trans ‐diaziridines, such as 1,2‐di‐ tert ‐butyldiaziridine ( 1 ) and 1,2‐di‐ n ‐butyldiaziridine ( 2 ) were determined. Enantioselective stopped‐flow multidimensional gas chromatography was used to investigate the enantiomerization barrier of 1 between 126.2 and 171.0 °C (Δ G (150.7 °C) = 135.8±0.2 kJ mol −1 , Δ H = 116.1±2.5 kJ mol −1 , Δ S = −46±2 J K −1 mol −1 ). The separation of the enantiomers has been achieved in presence of the chiral stationary phase (CSP) Chirasil‐ β ‐Dex with a high separation factor ( α = 1.44 at 80 °C). In a complementary approach, the enantiomerization barriers of 1,2‐di‐ tert‐ butyldiaziridine ( 1 ), 1,2‐di‐ n ‐butyldiaziridine ( 2 ), 1‐ n ‐butyl‐3,3‐dimethyldiaziridine ( 3 ), and 1,2,3,3‐tetramethyldiaziridine ( 4 ) were determined for comparison by enantioselective dynamic chromatography (DGC) and computer simulation of the dynamic elution profiles. The enantiomerization barrier of 2 was shown to be the highest among the nonsterically hindered diaziridines studied so far, whereas 1 exhibited the highest value found for strained nitrogen‐containing rings, that is, aziridines, diaziridines and oxaziridines.
Molecular Structure, Spectroscopy and Matrix Photochemistry of Fluorocarbonyl Iodide, FC(O)I
2004-02-16

Abstract The molecular structure of FC(O)I has been determined by gas electron diffraction. High‐level ab initio methods, including coupled‐cluster and the new correlation‐consistent basis sets for fourth row elements, have been used to calculate the structure of FC(O)I. A comprehensive vibrational spectroscopic study (both IR and Raman) complemented by high‐level calculations has also been performed. Furthermore, UV, mass, and NMR spectra have been recorded for FC(O)I. The matrix photochemistry of FC(O)I has been studied with a low‐pressure mercury lamp and with a high‐pressure xenon lamp in combination with interference and cut‐off filters. UV photolysis revealed the formation of the OC⋅⋅⋅IF and OC⋅⋅⋅FI complexes and further photolysis of these complexes at λ &gt;320 nm resulted in a re‐formation of FC(O)I. The structural conformation of the complexes has been characterized by comparing shifts in their CO and IF vibrational modes with respect to those of the free species. The structures, vibrational properties, and stability of the complexes were analyzed with the aid of coupled‐cluster ab initio calculations.
Synthesis of embedded systemC design: a case study of digital neural networks
2004-02-16

This work presents the whole system-on-silicon design flow using systemC system specification language. In this study, systemC is used to design a multilayer perceptron neural network, which is applied to an electrocardiogram pattern recognition system. The objective of this work is to exemplify the synthesis of RTL-and behavioral integrated systems. To achieve this, a preprocessing methodology was used to optimize the three main constraints of hardware neural network (HNN) design: accuracy, space and processing speed. This allows a complex HNN to be implemented on a single field programmable gate array (FPGA). The high level systemC synthesis allows the straightforward translation of system level into hardware level, avoiding the error prone and the time consuming translation into another hardware description language.