julilili42/papers huggingface dataset:
Functional relevance of ceruloplasmin mutations in Parkinson's Disease
2005-09-08

ABSTRACT Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo‐ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)‐linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo‐ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.
Towards a Framework and a Design Methodology for Autonomic SoC
2005-09-09

This paper proposes autonomic or organic computing principles to be applied to hardware design methods for future SoC solutions. Incorporating self-calibration, fault tolerance or even self-healing concepts into integrated circuit systems represents a major conceptual shift, which requires new design processes and tools. In the future, guarantee of functional correctness at the chip level will include self-configuration of adaptable components and flexible interfaces supporting a flexible component composition within complex SoC systems.
A Comparison of Financial Duration Models via Density Forecast
2005-09-09

Using density forecast evaluation techniques we compare the predictive performance of econometric specifications that have been developed for modeling duration processes in intra-day financial markets. The model portfolio encompasses various variants of the Autoregressive Conditional Duration (ACD) model and recently proposed dynamic factor models. The evaluation is conducted on time series of trade, price and volume durations computed from transaction data of NYSE listed stocks. The results show that simpler approaches perform at least as well as more complex methods. With respect to modeling trade duration processes, standard ACD models successfully account for duration dynamics whilst none of the models provides an acceptable specification for the conditional duration distribution. We find that the Logarithmic ACD, if based on a flexible innovation distribution, provides a quite robust and useful framework for the modeling of price and volume duration processes.
In Vitro Murein (Peptidoglycan) Synthesis by Dimers of the Bifunctional Transglycosylase-Transpeptidase PBP1B from Escherichia coli
2005-09-10

PBP1B is a major bifunctional murein (peptidoglycan) synthase catalyzing transglycosylation and transpeptidation reactions in Escherichia coli. PBP1B has been shown to form dimers in vivo. The K(D) value for PBP1B dimerization was determined by surface plasmon resonance. The effect of the dimerization of PBP1B on its activities was studied with a newly developed in vitro murein synthesis assay with radioactively labeled lipid II precursor as substrate. Under conditions at which PBP1B dimerizes, the enzyme synthesized murein with long glycan strands (>25 disaccharide units) and with almost 50% of the peptides being part of cross-links. PBP1B was also capable of synthesizing trimeric muropeptide structures. Tri-, tetra-, and pentapeptide compounds could serve as acceptors in the PBP1B-catalyzed transpeptidation reaction.
Neutrophil chemotaxis by pathogen-associated molecular patterns - formylated peptides are crucial but not the sole neutrophil attractants produced by Staphylococcus aureus
2005-09-12

The chemotactic migration of phagocytes to sites of infection, guided by gradients of microbial molecules, plays a key role in the first line of host defence. Bacteria are distinguished from eukaryotes by initiation of protein synthesis with formyl methionine. Synthetic formylated peptides (FPs) have been shown to be chemotactic for phagocytes, leading to the concept of FPs as pathogen-associated molecular patterns (PAMPs). However, it remains unclear whether FPs are major chemoattractants released by bacteria and whether further chemoattractants are produced. A Staphylococcus aureus mutant whose formyltransferase gene was inactivated (Deltafmt) produced no FPs and the in vitro and in vivo ability of Deltafmt culture supernatants to recruit neutrophils was considerably reduced compared with those of the parental strain. However, some chemotactic activity was retained, indicating that bacteria produce also unknown, non-FP chemoattractants. The activity of these novel PAMPs was sensitive to pertussis toxin but insensitive to the formyl peptide receptor inhibitor CHIPS. Deltafmt culture supernatants caused reduced calcium ion fluxes and reduced CD11b upregulation in neutrophils compared with wild-type supernatants. These data demonstrate an important role of FPs in innate immunity against bacterial infections and indicate that host chemotaxis receptors recognize a larger set of bacterial molecules than previously thought.
Towards a parity-dependent level density for astrophysics
2005-09-12

Astrophysical reaction rates are sensitive to the parity distribution at low excitation energies. We combine a formula for the energy-dependent parity distribution with a microscopic-macroscopic nuclear level density. This approach describes well the transition from low excitation energies where a single parity dominates to high excitations where the two densities are equal.
Effect of mitoxantrone on MRI in progressive MS
2005-09-13

In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.
Understanding Supported Reactions in Spherical Compartments:  A General Algorithm To Model and Determine Rate Constants, Diffusion Coefficients, and Spatial Product Distributions
2005-09-13

A general algorithm allowing the numerical modeling of the time and space dependence of product formation in spherical reaction volumes is described. The algorithm is described by the complete set of mass balance equations. On the basis of these equations, the effects of the diffusion coefficient, reaction rate, bead size, reagent excess, and packing density of the resin beads on the overall reaction rates are determined for second-order reactions. Experimental data of reaction progress are employed to calculate reaction rates and diffusion coefficients in polymer-supported reactions. In addition, the conditions for shell-like product formation are determined, and various strategies for the radial patterning of resin beads are compared. The effect of diffusion on polymer-supported enzyme-catalyzed reactions of the Michaelis-Menten type is treated, as well. Finally, the effects of typical nonideal solid-phase phenomena, namely, the inhomogeneity of rate constants and the concentration dependence of diffusion coefficients, on overall rates are discussed.
Dimensional crossover in Bragg scattering from an optical lattice
2005-09-14

We study Bragg scattering at 1D optical lattices. Cold atoms are confined by\\nthe optical dipole force at the antinodes of a standing wave generated inside a\\nlaser-driven high-finesse cavity. The atoms arrange themselves into a chain of\\npancake-shaped layers located at the antinodes of the standing wave. Laser\\nlight incident on this chain is partially Bragg-reflected. We observe an\\nangular dependence of this Bragg reflection which is different to what is known\\nfrom crystalline solids. In solids the scattering layers can be taken to be\\ninfinitely spread (3D limit). This is not generally true for an optical lattice\\nconsistent of a 1D linear chain of point-like scattering sites. By an explicit\\nstructure factor calculation we derive a generalized Bragg condition, which is\\nvalid in the intermediate regime. This enables us to determine the aspect ratio\\nof the atomic lattice from the angular dependance of the Bragg scattered light.\\n
CHARACTERIZATION AND DETECTION OF HEPATOCELLULAR CARCINOMA: COMPARISON BETWEEN THE ULTRASOUND CONTRAST AGENTS SONOVUE AND LEVOVIST: WHICH ONE IS BETTER?
2005-09-14

Purpose: SonoVue (Altana Pharma, Konstanz) and Levovist (Schering AG, Berlin) are both contrast agents, which are helpful in characterization and detection of malignant liver lesions. This study was performed to find out, which of both contrast agents is better in the diagnosis of hepatocellular carcinoma (HCC).
Inhibition of Natural Type I IFN-Producing and Dendritic Cell Development by a Small Molecule Receptor Tyrosine Kinase Inhibitor with Flt3 Affinity
2005-09-15

Abstract In vivo steady-state type I natural IFN-producing and dendritic cell (DC) development is largely dependent on Flt3 signaling. Natural IFN-producing and DC progenitors and their respective downstream cell populations express the flt3 receptor, and Flt3 ligand (Flt3L)−/− mice have reduced while Flt3L-injected mice develop markedly increased numbers of both cell types. In the present study, we show that SU11657, a small multitargeted receptor tyrosine kinase inhibitor with Flt3 affinity, suppressed in vitro natural IFN-producing and DC development in Flt3L-supplemented mouse whole bone marrow cell cultures in a dose-dependant manner, while DC development in GM-CSF-supplemented cultures was not affected. In vivo SU11657 application led to a significant decrease of both natural IFN-producing and DCs, comparable to the reduction observed in Flt3L−/− mice. Conversely, Flt3L plasma levels increased massively in inhibitor-treated animals, likely via a regulatory feedback loop, without being able to compensate for pharmacological Flt3 inhibition. No obvious toxicity was observed, and hemopoietic progenitor cell and stem cell function remained intact as assessed by myeloid colony-forming unit activity and in vivo bone marrow repopulation assays. Furthermore, upon treatment discontinuation, IFN-producing and DCs recovered to normal levels, proving that treatment effects were transient. Given the importance of IFN-producing and DCs in regulation of immune responses, these findings might lead to new pharmacological strategies in prevention and treatment of autoimmune diseases and complications of organ or blood cell transplantation.
Biosensors for unattended, cost-effective and continuous monitoring of environmental pollution: Automated Water Analyser Computer Supported System (AWACSS) and River Analyser (RIANA)
2005-09-15

This work describes our recent progress and achievements in the field of fully automated biosensors (Automated Water Analyser Computer Supported System (AWACSS) and River Analyser (RIANA)) for unattended, cost-effective and continuous monitoring of environmental pollution. We report on ultra-sensitive immunoassays for the hormones progesterone, testosterone and estrone and the pesticides propanil and isoproturon as examples of the outstanding progress made on biosensors in the field of environmental monitoring and water analysis. Most of the bio-active organic pollutants (estrone, progesterone, propanil and isoproturon) were detected at levels as low as 1.0pgm/L or even below. &lt;br/&gt;&lt;br/&gt;In fact, the reported limits of detection (LOD) were between 0.2 and 6.0pgm/L. For the first time, commercially available derivatives and antibodies were incorporated into immunoassays (progesterone and testosterone) for fully automated biosensors. To verify the assay performance for quantifying testosterone, progesterone, and isoproturon in real-world samples using our immunosensors, we spiked river and drinking water at six different levels from 0.9pgm/L to 90ngm/L. Nearly all recovery rates could be obtained between 70 and 120% as the AOAC International recommends it chiefly for water analysis.
Phage release from biofilm and planktonicStaphylococcus aureuscells
2005-09-16

The ability of pathogenic staphylococci to form biofilms facilitates colonization and the development of chronic infections. Therapy is hampered by the high tolerance of biofilms towards antibiotic treatment and the immune system. We found evidence that lysogenic Staphylococcus aureus cells in a biofilm and in planktonic cultures spontaneously release phages into their surroundings. Phages were detected over a much longer period in biofilm cultures than in planktonic supernatants because the latter were degraded by secreted proteases. Phage release in planktonic and biofilm cultures was artificially increased by adding mitomycin C. Two morphologically distinct phages in the S. aureus strain used in this work were observed by electron microscopy. We postulate that phage-release is a frequent event in biofilms. The resulting lysis of cells in a biofilm might promote the persistence and survival of the remaining cells, as they gain a nutrient reservoir from their dead and lysed neighboring cells. This might therefore be an early differentiation and apoptotic mechanism.
Automatic anatomical structures location based on dynamic shape measurement
2005-09-16

New image processing methods and active photonics apparatus have made possible the development of relatively inexpensive optical systems for complex shape and object measurements. We present dynamic 360° scanning method for analysis of human lower body biomechanics, with an emphasis on the analysis of the knee joint. The anatomical structure (of high medical interest) that is possible to scan and analyze, is patella. Tracking of patella position and orientation under dynamic conditions may lead to detect pathological patella movements and help in knee joint disease diagnosis. The processed data is obtained from a dynamic laser triangulation surface measurement system, able to capture slow to normal movements with a scan frequency between 15 and 30 Hz. These frequency rates are enough to capture controlled movements used e.g. for medical examination purposes. The purpose of the work presented is to develop surface analysis methods that may be used as support of diagnosis of motoric abilities of lower limbs. The paper presents algorithms used to process acquired lower limbs surface data in order to find the position and orientation of patella. The algorithms implemented include input data preparation, curvature description methods, knee region discrimination and patella assumed position/orientation calculation. Additionally, a method of 4D (3D + time) medical data visualization is proposed. Also some exemplary results are presented.
Antibiotic Chemotherapy of Onchocerciasis: In a Bovine Model, Killing of Adult Parasites Requires a Sustained Depletion of Endosymbiotic Bacteria (WolbachiaSpecies)
2005-09-19

Development of a drug lethal to adult Onchocerca volvulus (i.e., macrofilaricide) is a research priority for the control of human onchocerciasis. Using bovine O. ochengi infections, we investigated the effects of oxytetracycline administered in a short intensive regimen (SIR; 10 mg/kg daily for 14 days), compared with a prolonged intermittent regimen (PIR; 20 mg/kg monthly for 6 months) or a combination of both (COM), on the viability of adult worms and their endosymbiotic bacteria (Wolbachia species). The long-term treatments eliminated >80% (COM) or >60% (PIR) of adult female worms (P<.001), and the COM regimen effected a sustained depletion of Wolbachia organisms. Conversely, SIR was not macrofilaricidal and only transiently depleted Wolbachia densities, which repopulated worm tissues by 24 weeks after treatment. These results unequivocally demonstrate the macrofilaricidal potential of tetracyclines against Onchocerca infection and suggest that intermittent, protracted administration will be more effective than continuous shorter term treatment.
A noninvasive strategy for screening prospective blood donors for anemia
2005-09-19

BACKGROUND: The reliability of capillary hemoglobin (Hb) as an indicator for eligibility to donate blood is discussed controversially. Therefore, a noninvasive alternative with acceptable predictive values was established and evaluated. STUDY DESIGN AND METHODS: Donor candidates were selected according to their Hb level. The first donation was performed 6 weeks after this selection step. A venous blood sample was collected from all donors at the end of their donation and a postdonation Hb determination was performed. Donors with acceptable postdonation Hb values were permitted to donate next time without any predonation Hb measurement. Donors with low postdonation Hb values were permitted to donate only after a venous Hb measurement had shown an acceptable value. Sensitivity and specificity were determined by comparing the gold standard (i.e., venous Hb measurement) with the presented method of Hb estimation for 19,534 donors. RESULTS: Taking the postdonation Hb as an indicator for eligibility saved 97 percent of donors from being tested unnecessarily by capillary Hb measurement. This procedure resulted in a specificity of 92.6 percent and a sensitivity of 37.9 percent for Hb cutoff levels of 135 and 125 g per L for men and women, respectively. The sensitivity increased rapidly to 100 percent for Hb levels below 105 g per L. The average deviation from true Hb level was 6 g per L. CONCLUSION: The presented noninvasive method distinctly saves time and expenditure without endangering blood donors.
Conflict analysis in multiprocess synthesis for optimized system integration
2005-09-19

This paper presents a novel approach for multiprocess synthesis supporting well-tailored module integration at system level. The goal is to extend the local scope of existing architectural synthesis approaches in order to apply global optimization techniques across process bounds for shared system resources (e.g. memories, busses, global ALUs) during scheduling and binding. This allows an area efficient implementation of un-timed or cycle-fixed multiprocess specifications at RT or algorithmic level of abstraction. Furthermore, this approach supports environment-oriented synthesis for optimized module integration by scheduling accesses to global resources with respect to the access schedules of other modules communicating to the same global resources. As a result, dynamic access conflicts can be avoided by construction, and hence, there is no need for dynamic arbitration of bus and memory accesses with potentially unpredictable timing behavior.
Active succinate dehydrogenase (SDH) and lack of SDHD mutations in sporadic paragangliomas.
2005-09-20

Only two patients from our collective showed SDH gene mutations, one in SDHD and one in SDHB, respectively. Moreover, SDH activity detected in 5/8 patients confirmed the fact that SDH inactivation is not a major event in sporadic paragangliomas. LOH and FISH analysis demonstrated a frequent loss of regions within chromosome 11, indicating that additional genes in 11q may play a role in tumour genesis of sporadic paragangliomas.
Poly- N -Acetylglucosamine Production in Staphylococcus aureus Is Essential for Virulence in Murine Models of Systemic Infection
2005-09-21

ABSTRACT The contribution of the Staphylococcus aureus surface polysaccharide poly- N -acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin ( ica ) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA -deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.
Whole cell matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and in situ structure analysis of streptocidins, a family of tyrocidine‐like cyclic peptides
2005-09-21

Abstract Streptocidins, a family of tyrocidine‐like cyclic decapeptides, are an ideal demonstration object for the detection and in situ structure analysis of natural compounds directly in microbial cells using whole cell matrix‐assisted laser desorption/ionization time‐of‐flight‐mass spectrometry (MALDI‐TOFMS), an emerging technique that can be used for rapid sensitive metabolic profiling of microorganisms. Five main members of the streptocidin family (A–E) were detected in Brevibacillus cells picked from agar plates and identified by in situ structure analysis with post‐source decay MALDI‐TOFMS. This efficient modern method allows the precise detection of metabolites within minutes without the need to isolate and purify the target compounds. The generated mass spectra are of similar quality to those obtained for the purified peptides. In addition, surface extracts were prepared by treating Brevibacillus cells with 70% acetonitrile in the presence of 0.1% trifluoroacetic acid and fractionated by high‐resolution reversed‐phase high‐performance liquid chromatography (HPLC). In this way ten minor streptocidins were detected demonstrating the full biosynthetic variety of streptocidin production on the cellular level. The streptocidins differ from the well‐known tyrocidines essentially in position 3 of the decapeptide chain by replacement of the aromatic amino acid (F/W) found in tyrocidines by L ‐leucine or L ‐valine. Copyright © 2005 John Wiley &amp; Sons, Ltd.
Microcavity‐Controlled Single‐Molecule Fluorescence
2005-09-22

Abstract We present for the first time cavity‐controlled fluorescence spectra and decay curves of single dipole emitters interacting at room temperature with the first longitudinal mode of a Fabry–Perot microcavity offering a λ /2‐spacing between its silver mirrors. The spontaneous emission rate of individual dye molecules was found to be enhanced by the Purcell effect by up to three times compared to the rate in free space, in agreement with theoretical predictions. Moreover, our new microcavity design was found to provide long‐term stability and single‐molecule sensitivity under ambient conditions for several months without noticeable reduction of the cavity‐Q value. We consider this as a significant advance for single‐photon sources operating at room temperature.