julilili42/papers huggingface dataset:
The properties of phosphodiesterase 11A4 GAF domains are regulated by modifications in its N‐terminal domain
2008-02-27

The tandem GAF domain of human phosphodiesterase 11A4 (hPDE11A4) requires 72 μ m cGMP for half‐maximal effective concentration (EC 50 ) of a cyanobacterial adenylyl cyclase used as a reporter enzyme. Here we examine whether modifications in the N‐terminus of PDE11A4 affect cGMP signalling. The N‐terminus has two phosphorylation sites for cyclic nucleotide monophosphate‐dependent protein kinases (Ser117, Ser168). Phosphorylation of both by cAMP‐dependent protein kinase decreased the EC 50 value for cGMP from 72 to 23 μ m . Phosphomimetic point mutations (S117D/S167D), which project complete phosphorylation, lowered the EC 50 value to 16 μ m . Structural and sequence data indicate that 196 amino acids precede the start of the GAF domain in hPDE11A4. Removal of 197 amino acids yielded unregulated cyclase activity, whereas truncation by 196 amino acids resulted in a cGMP‐regulated protein with a cGMP EC 50 value of 7.6 μ m . Truncation by 176 amino acids was required for cGMP EC 50 values to decrease to below 10 μ m ; a construct truncated by 168 amino acids had an EC 50 value of 224 μ m . The decrease in EC 50 values was accompanied by a sixfold increase in basal activity; the extent of cGMP stimulation remained unaffected, however. We conclude that N‐terminal modifications strongly affect cGMP regulation of hPDE11A4.
Ultrasound‐guided injection of the iliopsoas muscle with botulinum toxin in camptocormia
2008-02-28

Abstract Camptocormia is characterized by an abnormal posture of the trunk with pronounced flexion of the thoraco‐lumbar spine during standing and walking, which abates in a supine position. Treatment options for camptocormia are limited and mostly futile. Here, we report on the ultrasound‐guided ventral injection of botulinum toxin A (BTX) into deep portions of the iliopsoas muscle in four parkinsonian patients with camptocormia as chief complaint. Using this novel and safe application technique, all patients received 500–1,500 MU of BTX per side in 4–6 month intervals. Treatment was generally well tolerated. At the highest dose, all patients complained of mild weakness of hip flexion. Standardized physical exam at follow‐up visits, as well as self‐assessment of patients, failed to show a relevant and lasting improvement of posture. In conclusion, injection of BTX into the iliopsoas does not appear to be a promising approach for the treatment of parkinsonism‐associated camptocormia. © 2008 Movement Disorder Society
Constraints on the magnetic field geometry of magnetars
2008-02-28

We study the effect of the magnetic field geometry on the oscillation spectra of strongly magnetized stars. The magnetic field distributions include both toroidal and poloidal contributions. We observe that the toroidal contribution does not influence significantly the torsional oscillations of the crust. Moreover, in the case that the core is a type I supercontactor and the magnetic fields are confined in the crust, the torsional oscillation spectrum is drastically affected by the presence of the strong magnetic fields. Comparison with results and estimations for the magnetic field strength, from observations, exclude the possibility that magnetars will have a magnetic field solely confined in the crust i.e. our results suggest that the magnetic field in whatever geometry has to permeate the whole star.
Incremental stress-strain relation from granular elasticity: Comparison to experiments
2008-02-28

Granular media are reversible and elastic if the stress increments are small enough. An elastic stress-strain relation, employed previously to determine static stress distributions, in this paper is compared to experiments by Kuwano and Jardine [Geotechnique 52, 727 (2002)] on incremental stress-strain relations, and shown to yield satisfactory agreement. In addition, the yield condition is given a firmer footing.
Sodium hyaluronate gels as a drug‐release system for corticosteroids: release kinetics and antiproliferative potential for glaucoma surgery
2008-02-28

Abstract. Purpose: To evaluate the release kinetics, biocompatibility and antiproliferative potential of a concentrated hydrophilic steroid formulation from commercially available sodium hyaluronate gels as a potential adjunct in glaucoma surgery. Methods: Dexamethasone and sodium hyaluronate 1% (Healon) and sodium hyaluronate 2.3% (Healon 5) were mixed to yield sodium hyaluronate formulations containing dexamethasone in concentrations of 4–20 mg/ml (7.7–38 m m ). Non‐cumulative and cumulative release into balanced salt solution (BSS) or phosphate buffered saline (PBS) was measured spectrophotometrically over 2–6 days. For cytotoxicity assays, human tenon fibroblasts (HTFB) and human retinal pigment epithelium cells (ARPE19) were cultured in a serum‐deficient medium to ensure a static milieu; 3‐(4,5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazoliumbromide (MTT) assay and Live/DeadTM cell‐mediated cytotoxicity assay were used to exclude cytotoxicity. Cellular proliferative activity was monitored by 5′‐bromo‐2′‐deoxyuridine (BrdU)‐incorporation into cellular DNA. Results: The release kinetics from sodium hyaluronate 1% and 2.3% were almost identical. Steady state was achieved after approximately 44 hrs in non‐cumulative measurements. The release plotted as a function of the square root of time was consistent with a largely diffusion‐controlled release system. No cytotoxicity could be observed. Dexamethasone‐loaded sodium hyaluronate showed a significant antiproliferative effect on HTFB and ARPE19 cells. Conclusion: Dexamethasone‐loaded sodium hyaluronate shows extended release of steroid over almost 2 days in concentrations high enough to inhibit the proliferation of HTFB and RPE cells without evoking cytotoxic effects. Thus, this formulation may be an easy‐to‐prepare adjunct in glaucoma surgery or other procedures in which cellular growth inhibition is desired.
Stabilizedin siturectangular MgB2wires: the effect of B purity and sheath materials
2008-02-28

Stabilized four-filament SiC-added in situ MgB2 wires were prepared by the rectangular wire-in-tube (RWIT) technique, using boron powders of different purity (90% and 99%), SiC powders of different agglomerate size and sheaths of different metals. The critical current density at 11 T and 4.2 K improved by 5–10 times by using boron powder of higher purity, SiC powder of small agglomerate size, a chemically inert Ti barrier and mechanical support provided by a Monel sheath. The decrease in critical temperature (Tc) and increase in critical current density (Jc) of wires could be explained in terms of carbon doping. Formation of Mg2Si and B-rich secondary phases, and carbon substitution was studied using EDX chemical mapping in a scanning electron microscope (SEM). The addition of SiC results in the formation of B-rich secondary phases. Our results support the mechanism of carbon doping through the reaction of SiC with Mg to form Mg2Si and release free carbon. However, the extent of effective carbon doping depends on the size of the precursor SiC agglomerates, as large SiC agglomerates are unable to react with Mg. B precursor powder of lower purity and Mg2Si secondary phase formation led to incomplete phase formation of MgB2 and consequently to lowered Jc.
Search for Subtelomeric Imbalances by Multiplex Ligation-Dependent Probe Amplification in Silver–Russell Syndrome
2008-02-28

Chromosomal aberrations are typically associated with primordial growth retardation, psychomotoric constrictions, and dysmorphisms. Since these features may be present in patients with Silver-Russell syndrome (SRS) and chromosomal disturbances are also detected in a subgroup of SRS patients, we screened a cohort of 45 SRS patients for cryptic subtelomeric imbalances. Submicroscopic deletions/duplications in the telomere regions are meanwhile well known to cause a broad spectrum of conspicuous phenotypes, characterized by mental retardation and multiple further congenital anomalies. We hypothesize that SRS might represent at the mild end of the broad phenotypic range of subtelomeric imbalances. Screening of the patients was performed by multiplex ligation-dependent probe amplification (MLPA), a technique that has already been shown to be effective and reliable for measuring copy numbers. We excluded pathogenetically relevant copy number variations in the subtelomeres in our SRS patient cohort, but one patient carried an apathogenic polymorphic Yq deletion. It can therefore be concluded that this type of chromosomal aberration does not belong to the genetic causes of SRS and it is not necessary to include this test in the diagnostic algorithm of the disease.
Automatic Cluster Detection in Kohonen's SOM
2008-02-29

Kohonen's self-organizing map (SOM) is a popular neural network architecture for solving problems in the field of explorative data analysis, clustering, and data visualization. One of the major drawbacks of the SOM algorithm is the difficulty for nonexpert users to interpret the information contained in a trained SOM. In this paper, this problem is addressed by introducing an enhanced version of the Clusot algorithm. This algorithm consists of two main steps: 1) the computation of the Clusot surface utilizing the information contained in a trained SOM and 2) the automatic detection of clusters in this surface. In the Clusot surface, clusters present in the underlying SOM are indicated by the local maxima of the surface. For SOMs with 2-D topology, the Clusot surface can, therefore, be considered as a convenient visualization technique. Yet, the presented approach is not restricted to a certain type of 2-D SOM topology and it is also applicable for SOMs having an n-dimensional grid topology.
Description of double β decay within the continuum quasiparticle random-phase approximation
2008-02-29

A method to calculate the nuclear double beta decay ( - and -) amplitudes within the continuum random phase approximation (cQRPA) is formulated. Calculations of the transition amplitudes within the cQRPA are performed for ^{76}Ge, ^{100}Mo and ^{130}Te. A rather simple nuclear Hamiltonian consisting of phenomenological mean field and zero-range residual particle-hole and particle-particle interaction is used. The calculated M^{2\\nu} are almost not affected when the single-particle continuum is taken into account. At the same time, a regular suppression of the -amplitude is found that can be associated with additional ground state correlations due to collective states in the continuum. It is expected that future inclusion of the nucleon pairing in the single-particle continuum will somewhat compensate the suppression.
Blocked Autophagy Sensitizes Resistant Carcinoma Cells to Radiation Therapy
2008-03-01

Abstract Autophagy or “self eating” is frequently activated in tumor cells treated with chemotherapy or irradiation. Whether autophagy represents a survival mechanism or rather contributes to cell death remains controversial. To address this issue, the role of autophagy in radiosensitive and radioresistant human cancer cell lines in response to γ-irradiation was examined. We found irradiation-induced accumulation of autophagosomes accompanied by strong mRNA induction of the autophagy-related genes beclin 1, atg3, atg4b, atg4c, atg5, and atg12 in each cell line. Transduction of specific target-siRNAs led to down-regulation of these genes for up to 8 days as shown by reverse transcription-PCR and Western blot analysis. Blockade of each autophagy-related gene was associated with strongly diminished accumulation of autophagosomes after irradiation. As shown by clonogenic survival, the majority of inhibited autophagy-related genes, each alone or combined, resulted in sensitization of resistant carcinoma cells to radiation, whereas untreated resistant cells but not sensitive cells survived better when autophagy was inhibited. Similarly, radiosensitization or the opposite was observed in different sensitive carcinoma cells and upon inhibition of different autophagy genes. Mutant p53 had no effect on accumulation of autophagosomes but slightly increased clonogenic survival, as expected, because mutated p53 protects cells by conferring resistance to apoptosis. In our system, short-time inhibition of autophagy along with radiotherapy lead to enhanced cytotoxicity of radiotherapy in resistant cancer cells. [Cancer Res 2008;68(5):1485–94]
Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses
2008-03-01

Abstract The tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhibitory effects are mediated by inhibition of PI3 and MAP kinases and NFκB signaling. In contrast, sorafenib had no influence on the phenotype and proliferation of T cells. To analyze the effects of both TKIs on cytotoxic T-cell induction in vivo, C57BL/6 mice were pretreated with sorafenib or sunitinib and immunized with OVA257-264 peptide. Sorafenib, but not sunitinib, application significantly reduced the induction of antigen-specific T cells. Numbers of regulatory T cells were reduced in peripheral blood mononuclear cells from mice treated with sunitinib. These results indicate that sunitinib, but not sorafenib, is suitable for combination with immunotherapeutic approaches for treatment of cancer patients.
Alfvén quasi-periodic oscillations in magnetars
2008-03-01

Abstract We investigate torsional Alfvén oscillations of relativistic stars with a global dipole magnetic field, via two-dimensional numerical simulations. We find that (i) there exist two families of quasi-periodic oscillations (QPOs) with harmonics at integer multiples of the fundamental frequency, (ii) the lower-frequency QPO is related to the region of closed field lines, near the equator, while the higher-frequency QPO is generated near the magnetic axis, (iii) the QPOs are long-lived, (iv) for the chosen form of dipolar magnetic field, the frequency ratio of the lower to upper fundamental QPOs is ∼0.6, independent of the equilibrium model or of the strength of the magnetic field, and (v) within a representative sample of equations of state and of various magnetar masses, the Alfvén QPO frequencies are given by accurate empirical relations that depend only on the compactness of the star and on the magnetic field strength. The lower and upper QPOs can be interpreted as corresponding to the edges or turning points of an Alfvén continuum, according to the model proposed by Levin (2007). Several of the low-frequency QPOs observed in the X-ray tail of SGR 1806-20 can readily be identified with the Alfvén QPOs we compute. In particular, one could identify the 18- and 30-Hz observed frequencies with the fundamental lower and upper QPOs, correspondingly, while the observed frequencies of 92 and 150 Hz are then integer multiples of the fundamental upper QPO frequency (three and five times, correspondingly). With this identification, we obtain an upper limit on the strength of the magnetic field of SGR 1806-20 (if is dominated by a dipolar component) between ∼3 and 7 × 1015 G. Furthermore, we show that an identification of the observed frequency of 26 Hz with the frequency of the fundamental torsional l= 2 oscillation of the magnetar's crust is compatible with a magnetar mass of about from 1.4 to 1.6 M⊙ and an equation of state (EOS) that is very stiff (if the magnetic field strength is near its upper limit) or moderately stiff (for lower values of the magnetic field).
Enhancement of long‐range EEG coherence by synchronous bifocal transcranial magnetic stimulation
2008-03-01

Abstract Interregional coupling of distant brain regions can be measured by electroencephalographic (EEG) coherence reflecting the spatial–temporal correlation between two oscillatory signals. It has been suggested that this coherence in activity is a signature of functional integration of multimodal neuronal networks. Repetitive transcranial magnetic stimulation (rTMS) is a well‐established technique for non‐invasive cortical stimulation. Its modulating effects outlast the train of stimulation and affect behavior. In the present study, we tested the hypothesis that cortico‐cortical coherence between distant brain areas can be selectively enhanced by synchronous bifocal rTMS. Cortico‐cortical coherence was assessed in 16 healthy human subjects before and after three trains of synchronous high‐frequency (10 Hz) rTMS to the left primary motor cortex and the visual cortex at the occipital pole simultaneously. Stimulation of the left M1 alone served as the control condition. Coherence and spectral power were measured between these areas on the stimulated and the homologue contralateral side. Synchronous bifocal rTMS induced an increase of interregional coupling in the alpha and lower beta band on the stimulated side without effects on spectral power. These data indicate that synchronous bifocal rTMS is a feasible technique for selective modulation of interregional EEG coherence. Furthermore, they raise the hypothesis that interventional enhancement of long‐range coherence may effectively modulate interregional integration with behavioral consequences.
Characterizing the N-Terminal Processing Motif of MHC Class I Ligands
2008-03-01

Abstract Most peptide ligands presented by MHC class I molecules are the product of an intracellular pathway comprising protein breakdown in the cytosol, transport into the endoplasmic reticulum, and successive N-terminal trimming events. The efficiency of each of these processes depends on the amino acid sequence of the presented ligand and its precursors. Thus, relating the amino acid composition N-terminal of presented ligands to the sequence specificity of processes in the pathway gives insight into the usage of ligand precursors in vivo. Examining the amino acid composition upstream the true N terminus of MHC class I ligands, we demonstrate the existence of a distinct N-terminal processing motif comprising approximately seven residues and matching the known preferences of proteasome and TAP, two key players in ligand processing. Furthermore, we find that some residues, which are preferred by both TAP and the proteasome, are underrepresented at positions immediately preceding the N terminus of MHC class I ligands. Based on experimentally determined aminopeptidase activities, this pattern suggests trimming next to the final N terminus to take place predominantly in the endoplasmic reticulum.
Natural water purification and water management by artificial groundwater recharge
2008-03-01

Worldwide, several regions suffer from water scarcity and contamination. The infiltration and subsurface storage of rain and river water can reduce water stress. Artificial groundwater recharge, possibly combined with bank filtration, plant purification and/or the use of subsurface dams and artificial aquifers, is especially advantageous in areas where layers of gravel and sand exist below the earth's surface. Artificial infiltration of surface water into the uppermost aquifer has qualitative and quantitative advantages. The contamination of infiltrated river water will be reduced by natural attenuation. Clay minerals, iron hydroxide and humic matter as well as microorganisms located in the subsurface have high decontamination capacities. By this, a final water treatment, if necessary, becomes much easier and cheaper. The quantitative effect concerns the seasonally changing river discharge that influences the possibility of water extraction for drinking water purposes. Such changes can be equalised by seasonally adapted infiltration/extraction of water in/out of the aquifer according to the river discharge and the water need. This method enables a continuous water supply over the whole year. Generally, artificially recharged groundwater is better protected against pollution than surface water, and the delimitation of water protection zones makes it even more save.
Cardioprotection and cardiac regeneration by mesenchymal stem cells.
2008-03-01

Mesenchymal stem cells (MSC) are promising candidates in the emerging field of regenerative medicine. MSC have been applied in numerous experimental and preclinical studies evaluating their therapeutical potential in various models of diseases. For cardiac applications, especially myocardial ischemia, MSC have been shown to provide an interesting therapeutical potential. However, to date the mechanisms of their beneficial effects on the cardiac tissue are only faintly elucidated. On the one hand we do not completely understand the biology of the MSC, on the other hand their interactions with the complex in vivo situation e. g. after myocardial infarction and the following remodeling processes are difficult to study. Initially, with respect to their in vitro differentiation capacity, it has been assumed that transplanted MSC may, promoted by the local microenvironment, differentiate in vivo into cells of cardiomyogenic phenotype or even cardiomyocytes, integrate themselves into the myocardium and help to regenerate the damaged tissue. The finding that after transplantation only a minor percentage of the MSC showed long term survival and persistent lack of evidence for in vivo differentiation make the original mechanistic concept of in vivo cardiomyogenic differentiation questionable. More recent studies suggest that the transplanted MSC may interact with the local tissue releasing paracrine factors and may hereby support the regenerative process. In this article, referring to experimental and preclinical studies, characteristics, sources, differentiation and paracrine activity of MSC contributing to cardioprotection and cardiac regeneration will be discussed.
IMAGE-GUIDED LATERAL SUBOCCIPITAL APPROACH
2008-03-01

Volumetric image guidance provides fast and reliable three-dimensional visualization of sinus anatomy in the posterior fossa, thereby significantly increasing speed and safety in lateral suboccipital approaches.
Simultaneity
2008-03-01

Observer Perspectives: Epistemological Background: Fractal Time: Extended Observer Perspectives (S Vrobel) Mirror Neurons: Evidence for the Great Simulator and Vrobelism (O E Rossler) Brain Time and Physical Time (U Fidelman) Identifying Temporal Observer Perspectives: On Time Experience in Depression (H M Emrich et al.) Ordinate Logics of Living Systems (J L R Chandler) Utilizing Fractal Time (T Marks-Tarlow) Disentangling Temporal Simultaneous Contrasts: Simultaneity in Emotional Moments (G L Clore) Application of an Endo-Perspective of Temporal Structures (L Nottale & P Timar) Modeling Common-Sense Decisions (M Zak) Synchronization: Computer Simulations as Hidden Time Ecologies (G Koehler) Anti-Flaring: How to Prevent the Market from Overheating (A P Schmidt & O E Rossler) Endonomics: Looking Behind the Economic Curtain (A P Schmidt & O E Rossler) and other papers.
Panton‐Valentine Leukocidin‐Producing Methicillin‐SensitiveStaphylococcus aureusas a Cause for Recurrent, Contagious Skin Infections in Young, Healthy Travelers Returned From a Tropical Country: A New Worldwide Public Health Problem?
2008-03-01

Skin infections associated with visits to tropical countries are well known. In most of the cases, the infection is caused by Staphylococcus aureus. After a sufficient antibiotic treatment, the skin infections resolve without any sequelae. But several patients suffer from recurrent skin infections. Panton‐Valentine leukocidin (PVL) is a cytotoxin produced by S aureus, which is associated with severe necrotic skin lesions and with a high contagiosity.