julilili42/papers huggingface dataset:
Hyperphosphorylation and Aggregation of Tau in Experimental Autoimmune Encephalomyelitis
2004-10-20

Axonal damage is a major morphological correlate and cause of permanent neurological deficits in patients with multiple sclerosis (MS), a multifocal, inflammatory and demyelinating disease of the central nervous system. Hyperphosphorylation and pathological aggregation of microtubule-associated protein tau is a common feature of many neurodegenerative diseases with axonal degeneration including Alzheimer's disease. We have therefore analyzed tau phosphorylation, solubility and distribution in the brainstem of rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Tau was hyperphosphorylated at several sites also phosphorylated in Alzheimer's disease and became partially detergent-insoluble in EAE brains. Morphological examination demonstrated accumulation of amorphous deposits of abnormally phosphorylated tau in the cell body and axons of neurons within demyelinating plaques. Hyperphosphorylation of tau was accompanied by up-regulation of p25, an activator of cyclin-dependent kinase 5. Phosphorylation of tau, activation of cdk5, and axonal pathology were significantly reduced when diseased rats were treated with prednisolone, a standard therapy of acute relapses in MS. Hyperphosphorylation of tau was not observed in a genetic or nutritional model of axonal degeneration or demyelination, suggesting that inflammation as detected in the brains of rats with EAE is the specific trigger of tau pathology. In summary, our data provide evidence that axonal damage in EAE and possibly MS is linked to tau pathology.
Determination of ZnO(0001) surface termination by x‐ray photoelectron spectroscopy at photoemission angles of 0° and 70°
2004-10-20

Abstract We present an XPS method to determine the termination of the ZnO(0001) surface. By measuring O 1s and Zn 2p 3/2 core‐level x‐ray photoelectron spectra at photoemission angles of 0° and 70° and comparing the intensity ratio ( I O1s / I Zn2p3 ) θ=0 /( I O1s / I Zn2p3 ) θ=70 , the Zn and O termination can be distinguished. Calculations show that these two terminations have intensity ratios differing by ∼17%. This difference is not affected by a contamination layer provided that the contamination layer thickness is the same for these two differently terminated surfaces. Although this determination method prefers a clean ZnO(0001) surface ( in situ measurement), it seems also feasible for surfaces with known contamination layer thickness ( ex situ measurement). We have measured ex situ ZnO(0001)‐Zn, ZnO(000&amp;#38;1macr;)‐O single crystals and an epitaxial ZnO film deposited on Al 2 O 3 (0001). The measured intensity ratios of the first two samples agree with the calculated values for a 0.2 and 0.26 nm contamination layer, respectively. The intensity ratio and the O 1s contamination component intensity of the epitaxial ZnO film are close to those of the ZnO(0001)‐Zn single crystal thus pointing at Zn termination of the film. Copyright © 2004 John Wiley &amp; Sons, Ltd.
Identification of a naturally processed cyclin D1 T‐helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry
2004-10-20

Abstract T‐helper (Th) cells play an important role in orchestrating the effector function of CTL in anti‐tumor immunity. However, only a limited number of Th cell epitopes has been characterized. Here we describe a novel approach for identifying naturally processed and presented peptides derived from chosen antigens. This method combines a transfection step of antigen‐presenting cells with a vector encoding a fusion protein between the Ii chain and the antigen of interest, elution of the HLA‐bound peptides and identification of the antigen‐derived peptides by mass spectrometric comparison to the non‐transfected cells. In vitro ‐stimulated Th cells against the identified peptide of interest specifically recognize transfectants overexpressing the cognate antigen. Using this approach, we were able to identify the HLA‐DR4‐restricted Th cell epitope NPPSMVAAGSVVAAV derived from cyclin D1, which is frequently overexpressed in tumors. This method will help in identifying peptide candidates for vaccination studies for tumor immunotherapy.
Adhesion forces measured at the level of a terminal plate of the fly's seta
2004-10-21

The attachment pads of fly legs are covered with setae, each ending in small terminal plates coated with secretory fluid. A cluster of these terminal plates contacting a substrate surface generates strong attractive forces that hold the insect on smooth surfaces. Previous research assumed that cohesive forces and molecular adhesion were involved in the fly attachment mechanism. The main elements that contribute to the overall attachment force, however, remained unknown. Multiple local force-volume measurements were performed on individual terminal plates by using atomic force microscopy. It was shown that the geometry of a single terminal plate had a higher border and considerably lower centre. Local adhesion was approximately twice as strong in the centre of the plate as on its border. Adhesion of fly footprints on a glass surface, recorded within 20 min after preparation, was similar to adhesion in the centre of a single attachment pad. Adhesion strongly decreased with decreasing volume of footprint fluid, indicating that the layer of pad secretion covering the terminal plates is crucial for the generation of a strong attractive force. Our data provide the first direct evidence that, in addition to Van der Waals and Coulomb forces, attractive capillary forces, mediated by pad secretion, are a critical factor in the fly's attachment mechanism.
Fractality in geology: a possible use of fractals in the studies of partial melting processes
2004-10-23

The use of nonlinear and chaotic dynamics and fractal approaches in the studies of the Earth has increased in the last decade.A large number of geological objects show a power-law or fractal distribution, which suggests that these objects do not require any characteristic length-scale or time in their definition.Fractals can be used in studies of magma mixing and mingling, mantle convection, lava flows, percolation properties of veins and ore mineralization, and to separate geochemical anomalies.It is shown that the width of migmatitic leucosomes in the Estonian basement rock follows power-law distributions and shows fractal properties.Despite the differences in size and number of measured leucosomes and veins, differences in host rock types and formation conditions, the studied leucosome and vein data set shows good power-law distributions with exponents, m, usually between 1.0 and 1.9.The spacing of leucosomes and veins in rock section is not a random feature, but fractal (fractal dimension D = 0.77-0.79).Using the power-law size distribution for the melt batches, the total volume of the melt phase, as well as the relative contributions of the largest batch (dominant for m < 1) and of the smallest batches (dominant for m > 1), are estimated.The relationship between the magmatic leucosome width-distribution exponent, and the melt batch size-distribution is derived.
3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency in an adult with leukoencephalopathy
2004-10-25

Abstract 3‐Hydroxy‐3‐methylglutaryl‐CoA lyase deficiency is a disorder of leucine metabolism that usually presents with recurrent episodes of life‐threatening hypoglycemia during early childhood. We report on a 36‐year‐old woman with seizures, recurrent metabolic disturbances, and severe leukoencephalopathy. The diagnosis was made by analysis of amino acids in urine and serum and was confirmed by demonstration of the deficient enzyme in cultured skin fibroblasts. The patient improved clinically on oral L ‐carnitine substitution. This treatable condition can remain unrecognized in adults and should be considered a potential cause of leukoencephalopathy. Ann Neurol 2004;56:727–730
Global Risk Management in Type 2 Diabetes: Blood Glucose, Blood Pressure, and Lipids - Update on the Background of the Current Guidelines
2004-10-25

Diabetes mellitus presents a significant public health burden based on its increased morbidity, mortality, and economic cost. The high comorbidity and prevalence of concomitant diseases like hypertension and dyslipidemia in diabetic patients cause the high risk in developing secondary, cost intensive, and for the patient often disastrous late complications (nephropathy, retinopathy, neuropathy, and cardiovascular disease). Therefore, patients with diabetes mellitus need a global risk management that takes the various individual clinical problems into account. The current global standards of therapy in patients with diabetes mellitus are focused on the control of glycemia, blood pressure, and lipid levels, as well as aspirin therapy and avoiding of smoking. There are a number of guidelines and recommendations to manage these global issues. Our review will summarize current recommendations and consolidate therapeutic goals and treatments that are of vital importance in the global risk management in diabetic patients.
Who Owns the Internet? Ownership as a Legal Basis for American Control of the Internet
2004-10-25

The U.S. government's ultimate control of the Domain Name System results in substantial power over the entire Internet. Other countries object to this American dominance and demand that control of the Internet be handed over to the UN or the ITU. The United States could have a legal claim for control based on ownership because the Internet is, or was at least originally, an American thing, invented and funded by the United States. The paper examines such an ownership idea by applying property and intellectual property law on both the American and the international level. An examination of ownership is crucial because other approaches that could provide a legal basis for special power, like sovereignty, face problems because U.S. sovereignty ends at its borders and conflicts with the sovereignty of other states that are affected by U.S. policy decisions about the Internet.
Three-periodic nets and tilings: minimal nets
2004-10-26

The 15 3-periodic minimal nets of Beukemann & Klee [Z. Kristallogr. (1992), 201, 37-51] have been examined. Seven have collisions in barycentric coordinates and are self-entangled. The other eight have natural tilings. Five of these tilings are self-dual and the nets are the labyrinth nets of the P, G, D, H and CLP minimal surfaces of genus 3. Twelve ways have been found for subdividing a cube into smaller tiles without introducing new vertices. Duals of such tilings with one vertex in the primitive cell have nets that are one of the minimal nets. Minimal nets without collisions are uniform.
Rare, Highly Pyrimethamine‐Resistant Alleles of thePlasmodium falciparumDihydrofolate Reductase Gene from 5 African Sites
2004-10-26

In eastern and southern Africa, there has been a rapid increase in the prevalence of alleles with mutations in the Plasmodium falciparum dihydrofolate reductase gene (dhfr) associated with increased risk of clinical failure of sulfadoxine-pyrimethamine (S/P). Molecular methods for surveillance of these mutations are now widespread, but the usual analysis detects only the most prevalent allele in a polyclonal sample. We used a yeast-expression system to identify rare, highly pyrimethamine-resistant alleles of dhfr in isolates from 5 African countries--Kenya, Tanzania, Malawi, Gabon, and Nigeria. Only the isolates from Nigeria yielded significant numbers of novel resistant alleles, and only 1 of the alleles from any location showed a >3-fold increase in resistance to S/P or to chlorproguanil-dapsone. Overall, these results suggest that dhfr alleles that confer high levels of resistance to antifolates are rare, even in eastern and southern Africa, where pyrimethamine has been intensively used.
Significance of the endothelin ETA receptor in the haemodynamic and inotropic effects of endothelin-1 in rats
2004-10-26

The main aim of the present study was to investigate the direct inotropic effects of stimulation of the endothelin (ET) receptor ETA under in vivo conditions. It is well known that ETA receptor stimulation causes pronounced vasoconstriction. The ET-1-induced coronary vasoconstriction may lead to myocardial ischaemia and, consequently, to cardiodepressor effects that may mask the direct positive inotropic effect of ETA receptor stimulation. Thus, in the present study, steps were taken to avoid this possibility. In anaesthetized open-chest rats the haemodynamic and inotropic effects of ETA receptor stimulation were studied by monitoring responses evoked by ET-1 (1 nmol/kg of body weight) after ETB receptor blockade with BQ 788 (0.5 μmol/kg of body weight); these responses were compared with saline controls (after ETB receptor blockade). To avoid vasoconstrictor effects induced by ETA receptor stimulation, additional experiments were performed in the presence of the vasodilator adenosine (2.0 mg·kg−1 of body weight·min−1). Myocardial function was also examined during aortic clamping so as to circumvent the effect of changes in afterload. We studied further the effect of ETA receptor stimulation on myocardial energy metabolism. ETA receptor stimulation reduced cardiac output (−49% compared with control), raised total peripheral resistance (+173%) and reduced myocardial ATP content (−23%). Aortic clamping did not reveal a positive inotropic effect of ETA receptor stimulation. Furthermore, even though adenosine attenuated the decrease in cardiac output (−21%), the increase of total peripheral resistance (+48%) and prevented the fall of myocardial ATP content (+6%), this did not unmask a positive inotropic effect of ETA receptor stimulation. Thus we conclude that ETA receptor stimulation causes vasoconstriction and myocardial ischaemia, but has no positive inotropic effects in rats.
A Unique Hydrophobic Cluster Near the Active Site Contributes to Differences in Borrelidin Inhibition among Threonyl-tRNA Synthetases
2004-10-27

Borrelidin, a compound with anti-microbial and anti-angiogenic properties, is a known inhibitor of bacterial and eukaryal threonyl-tRNA synthetase (ThrRS). The inhibition mechanism of borrelidin is not well understood. Archaea contain archaeal and bacterial genre ThrRS enzymes that can be distinguished by their sequence. We explored species-specific borrelidin inhibition of ThrRSs. The activity of ThrRS from Sulfolobus solfataricus and Halobacterium sp. NRC-1 was inhibited by borrelidin, whereas ThrRS enzymes from Methanocaldococcus jannaschii and Archaeoglobus fulgidus were not. In Escherichia coli ThrRS, borrelidin binding induced a conformational change, and threonine was not activated as shown by ATP-PP(i) exchange and a transient kinetic assay measuring intrinsic tryptophan fluorescence changes. These assays further showed that borrelidin is a noncompetitive tight binding inhibitor of E. coli ThrRS with respect to threonine and ATP. Genetic selection of borrelidin-resistant mutants showed that borrelidin binds to a hydrophobic region (Thr-307, His-309, Cys-334, Pro-335, Leu-489, Leu-493) proximal to the zinc ion at the active site of the E. coli ThrRS. Mutating residue Leu-489 --> Trp reduced the space of the hydrophobic cluster and resulted in a 1500-fold increase of the K(i) value from 4 nM to 6 microm. An alignment of ThrRS sequences showed that this cluster is conserved in most organisms except for some Archaea (e.g. M. jannaschii, A. fulgidus) and some pathogens (e.g. Helicobacter pylori). This study illustrates how one class of natural product inhibitors affects aminoacyl-tRNA synthetase function, providing potentially useful information for structure-based inhibitor design.
Safe and Reliable Sound Threshold Measures with Direct Vibration of the Ossicular Chain
2004-10-27

Abstract Objectives: The aim of the study was to evaluate the safety and feasibility of piezoelectric malleus vibration audiometer (MVA), which presents micromechanical vibrations to the umbo membranae tympani. Study Design: Phase I study performed in a tertiary referral center (University Hospital). Methods: The coupling rod of the MVA was moved slowly through the outer ear canal toward the eardrum with a micromanipulator. Coupling was completed when the rod tip touched the umbo membranae tympani. Basic audiologic measures of sound threshold obtained with direct stimulation of the malleus are presented. We used MANOVA (multivariate repeated measures ANOVA) to investigate the repeatability of MVA thresholds from one day to the other and when decoupling and retracting the coupling rod 2 mm off the umbo. We also selected the MANOVA to test for unwanted bone‐conduction threshold shifts after MVA application. We assessed normality of the data by quantile‐quantile plots of the residuals. Results: Twenty‐eight male and 10 female subjects with normal hearing, 22.2 to 34.6 years old (median age, 27.2 yr) underwent an examination. Thirty‐six subjects underwent MVA, because 2 of the 38 subjects who volunteered for the study have not undergone the procedure due to the external auditory canal anatomy preventing application of the MVA. The results show that it is possible to safely and reliably measure thresholds of direct vibration of the ossicular chain. Using pure tone audiograms, no pure tone bone‐ and/or air‐conduction threshold shifts occurred after the procedure. None of the subjects reported any other ear‐related symptoms such as vertigo, tinnitus, or dizziness. Geometric mean vibratory displacements at threshold ranged from 0.55 nm at 250 Hz to 0.03 nm at 6 kHz. MANOVA demonstrated a repeatability of MVA thresholds. Conclusion: Malleus vibration audiometry will not allow exact linkage of actual implantable hearing aid. But the present study demonstrates that MVA can provide an audiometric tool for assessing ossicular function and integrity prior to implantation of an electronic hearing amplifier.
A PINOID-Dependent Binary Switch in Apical-Basal PIN Polar Targeting Directs Auxin Efflux
2004-10-28

Polar transport–dependent local accumulation of auxin provides positional cues for multiple plant patterning processes. This directional auxin flow depends on the polar subcellular localization of the PIN auxin efflux regulators. Overexpression of the PINOID protein kinase induces a basal-to-apical shift in PIN localization, resulting in the loss of auxin gradients and strong defects in embryo and seedling roots. Conversely, pid loss of function induces an apical-to-basal shift in PIN1 polar targeting at the inflorescence apex, accompanied by defective organogenesis. Our results show that a PINOID-dependent binary switch controls PIN polarity and mediates changes in auxin flow to create local gradients for patterning processes.
Identification of neon in FUSE and VLT spectra of extremely hot hydrogen-deficient (pre-) white dwarfs
2004-10-28

\\n One of the strongest absorption lines observed in far-ultraviolet\\nFUSE spectra of many PG 1159 stars remained unidentified up to now. We show that\\nthis line, located at 973.3 Å, stems from . We also present new\\noptical high-resolution spectra of PG 1159 stars, obtained with the ESO VLT,\\nwhich cover the 3644 Å line and a newly identified \\nmultiplet in the 3850–3910 Å region. \\nWe compare the observed neon lines with NLTE models and conclude a\\n substantial neon overabundance in a number of objects. Although a detailed\\n analysis is still to be performed in order to compare quantitatively the\\n abundances with evolutionary theory predictions, \\nthis\\ncorroborates the idea that the PG 1159 stars and their immediate progenitors, the\\n[WC]-type nuclei of planetary nebulae, display intershell matter of their\\nprecursor AGB stars. Possibly as the consequence of a late He-shell flash, H-deficient\\nand (s-processed) Fe-depleted matter, that is strongly enriched by\\n3α-processed elements (C, O, Ne), is dredged up to the surface. Hence, a\\ndetailed study of the element abundance patterns in these peculiar stars gives\\nthe unique possibility to probe mixing and nucleosynthesis processes in\\nthe precursor AGB stars.\\n\\n\\n
Optical multiphoton lattices
2004-10-29

We propose a scheme that allows us to Fourier-synthesize arbitrarily shaped periodic potentials for atoms. The method is based on the dispersion connected with higher order multiphoton Raman processes, where a suitable combination of laser frequencies eliminates unwanted standing wave effects. Future application of the scheme could range from blazed atomic beam splitters up to atomic quantum ratchets.
Transmembrane transcriptional control (surface signalling) of theEscherichia coliFec type
2004-10-30

The ferric citrate transport system of Escherichia coli is the first example of a transcription initiation mechanism that starts at the cell surface. The inducer, ferric citrate, binds to an outer membrane transport protein, and without further transport elicits a signal that is transmitted across the outer membrane, the periplasm, and the cytoplasmic membrane into the cytoplasm. Signal transfer across the three subcellular compartments is mediated by the outer membrane transport protein that interacts in the periplasm with a cytoplasmic transmembrane protein. The latter is required for activation of a sigma factor which belongs to the extracytoplasmic function sigma factor family. A similar kind of transcription regulation has been demonstrated in Pseudomonas putida, P. aeruginosa, Serratia marcescens, Klebsiella pneumoniae, Aerobacter aerogenes, Bordetella pertussis, B. bronchseptica, B. avium, and Ralstonia solanacearum. The genomes of P. putida, P. aeruginosa, Nitrosomonas europaea, Bacteroides thetaiotaomicron and Caulobacter crescentus predict the existence of many more such transcriptional regulatory devices.
SD-208, a Novel Transforming Growth Factor β Receptor I Kinase Inhibitor, Inhibits Growth and Invasiveness and Enhances Immunogenicity of Murine and Human Glioma CellsIn vitroandIn vivo
2004-11-01

Abstract The cytokine transforming growth factor (TGF)-β, by virtue of its immunosuppressive and promigratory properties, has become a major target for the experimental treatment of human malignant gliomas. Here we characterize the effects of a novel TGF-β receptor (TGF-βR) I kinase inhibitor, SD-208, on the growth and immunogenicity of murine SMA-560 and human LN-308 glioma cells in vitro and the growth of and immune response to intracranial SMA-560 gliomas in syngeneic VM/Dk mice in vivo. SD-208 inhibits the growth inhibition of TGF-β–sensitive CCL64 cells mediated by recombinant TGF-β1 or TGF-β2 or of TGF-β–containing glioma cell supernatant at an EC50 of 0.1 μmol/L. SD-208 blocks autocrine and paracrine TGF-β signaling in glioma cells as detected by the phosphorylation of Smad2 or TGF-β reporter assays and strongly inhibits constitutive and TGF-β–evoked migration and invasion, but not viability or proliferation. Peripheral blood lymphocytes or purified T cells, cocultured with TGF-β–releasing LN-308 glioma cells in the presence of SD-208, exhibit enhanced lytic activity against LN-308 targets. The release of interferon γ and tumor necrosis factor α by these immune effector cells is enhanced by SD-208, whereas the release of interleukin 10 is reduced. SD-208 restores the lytic activity of polyclonal natural killer cells against glioma cells in the presence of recombinant TGF-β or of TGF-β–containing glioma cell supernatant. The oral bioavailability of SD-208 was verified by demonstrating the inhibition of TGF-β–induced Smad phosphorylation in spleen and brain. Systemic SD-208 treatment initiated 3 days after the implantation of SMA-560 cells into the brains of syngeneic VM/Dk mice prolongs their median survival from 18.6 to 25.1 days. Histologic analysis revealed no difference in blood vessel formation, proliferation, or apoptosis. However, animals responding to SD-208 showed an increased tumor infiltration by natural killer cells, CD8 T cells, and macrophages. These data define TGF-β receptor I kinase inhibitors such as SD-208 as promising novel agents for the treatment of human malignant glioma and other conditions associated with pathological TGF-β activity.