julilili42/papers huggingface dataset:
Low dose continuous oral and transdermal hormone therapy and effects on biochemical marker for vascular tone and inflammation
2008-09-01

Objectives: To compare the effect of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) in terms of cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri. Methods: Patients were randomized to receive either transdermal E2/NETA (delivering daily doses of E2 25μg and NETA 125μg; applied every 3–4 days) or oral E2/NETA (E2 1mg and NETA 0.5mg; given daily) in this open-label study. Assessment of the following markers or their stable metabolites in serum or urine: P-selectin, ICAM–1, VCAM–1, MCP–1, MMP–9, homocysteine, cGMP, serotonin, prostacyclin, thromboxane, and urodilatin. Results: Significant decreases were found for P-selectin, ICAM–1, MCP–1 and homocysteine for both HRT regimens as compared to baseline. MMP–9 was increased only by oral HRT. The urinary concentrations of cGMP, the ratio of prostacyclin to thromboxane metabolite and the serotonin metabolite were significantly increased for both HRT application modes although the oral application showed a significantly greater increase than the transdermal one with respect to baseline. Urodilatin excretion was only increased by the oral regimen. Conclusions: Low-dose transdermal and oral HRT using estradiol and norethisterone acetate elicit favourable effects on cardiovascular biochemical markers. For most marker the changes found were in a similar magnitude with respect to baseline, however, in some cases oral HRT led to a significant higher alteration while in other cases the transdermal formulations seems to provide greater benefits.
Exchange Rates and FDI: Goods versus Capital Market Frictions
2008-09-01

ABSTRACT Changes in exchange rates affect countries through their impact on cross‐border activities such as trade and foreign direct investment (FDI). With increasing activities of multinational firms, the FDI channel is likely to gain in importance. Economic theory provides two main explanations why changes in exchange rates can affect FDI. According to the first explanation, FDI reacts to exchange rate changes if there are information frictions on capital markets and if investment depends on firms’ net worth (capital market friction hypothesis). According to the second explanation, FDI reacts to exchange rate changes if output and factor markets are segmented, and if firm‐specific assets are important (goods market friction hypothesis). We provide a unified theoretical framework of these two explanations. We analyse the implications of the model empirically using a dataset based on detailed German firm‐level data. We find greater support for the goods market than for the capital market friction hypothesis.
ChemInform Abstract: Organic Molecular Beam Deposition: Fundamentals, Growth Dynamics, and in situ Studies
2008-09-02

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Targeting the Ribose and Phosphate Binding Site of p38 Mitogen-Activated Protein (MAP) Kinase: Synthesis and Biological Testing of 2-Alkylsulfanyl-, 4(5)-Aryl-, 5(4)-Heteroaryl-Substituted Imidazoles
2008-09-03

Three series of substituted 2-alkylsulfanyl-4-(4-fluorophenyl)imidazoles, 5-pyridinyl-, 1-methyl-5-pyridinyl-, and 5-(2-aminopyridin-4-yl)-imidazoles, were prepared and tested for their ability to inhibit p38 MAP kinase and TNF-alpha release. These compounds were prepared by using different synthetic routes. They were tested by applying a nonradioactive p38 MAP kinase assay and by measurement of TNF-alpha release in human whole blood. Potent inhibitors (IC50 values in the low nanomolar range, as low as 2 nM in the enzyme assay and 37 nM in the human whole blood test) were identified by variation of substituents at the imidazole- C2-thio position as well as at the 2-aminopyridinyl functionality. In contrast to other known kinase inhibitors, these novel imidazole derivatives with the substituents at the imidazole-C2-thio position may interact with the ribose as well as with the phosphate binding site of the p38 MAP kinase.
Measuring diffusion with polarization-modulation dual-focus fluorescence correlation spectroscopy
2008-09-03

We present a new technique, polarization-modulation dual-focus fluorescence correlation spectroscopy (pmFCS), based on the recently intro-duced dual-focus fluorescence correlation spectroscopy (2fFCS) to measure the absolute value of diffusion coefficients of fluorescent molecules at pico- to nanomolar concentrations. Analogous to 2fFCS, the new technique is robust against optical saturation in yielding correct values of the diffusion coefficient. This is in stark contrast to conventional FCS where optical saturation leads to an apparent decrease in the determined diffusion coefficient with increasing excitation power. However, compared to 2fFCS, the new technique is simpler to implement into a conventional confocal microscope setup and is compatible with cw-excitation, only needing as add-ons an electro-optical modulator and a differential interference contrast prism. With pmFCS, the measured diffusion coefficient (D) for Atto655 maleimide in water at 25?C is determined to be equal to (4.09 +/- 0.07) x 10(-6)cm(2)/s, in good agreement with the value of 4.04 x 10-6cm2/s as measured by 2fFCS.
Probing dielectric interfaces on the nanoscale with elastic scattering patterns of single gold nanorods
2008-09-03

We study spatially isolated, individual gold nanorods placed at a planar interface between two dielectric media using confocal interference scattering microscopy in combination with higher order laser modes. Approaching refractive index matching conditions, we observe that the elastic scattering patterns of individual nanorods exhibit an exponential increase of both the scattering intensity and the signal-to-background ratio. In case refractive index matching conditions are fullfilled, the data acquisition rates are maximized and suitable for in-vivo biological measurements. In all cases, the characteristic two-lobe shape of the scattering patterns of single nanorods remains unchanged while the sign of the image contrast is a direct consequence of the refractive index variation occurring at the interface.
Prevention of Polymorphic Light Eruption with a Sunscreen of Very High Protection Level Against UVB and UVA Radiation Under Standardized Photodiagnostic Conditions
2008-09-03

Polymorphic light eruption (PLE), with an overall prevalence of 10-20%, is mainly provoked by ultraviolet A (UVA) (320-400 nm) and to a lesser degree by UVB (280-320 nm). The most effective prophylaxis of PLE, application of UV protection clothing, is not feasible for all sun-exposed areas of the skin and UV-hardening is time-consuming and may be associated with side-effects. Most sunscreens protect predominantly against UVB and therefore fail to prevent PLE. The protection level of potent UVA-protective filters remains unresolved. This single-centre, open, placebo-controlled, intra-individual, comparative study, analysed the efficacy of a sunscreen of very high protection level against UVB and UVA, containing methylene bis-benzotriazolyl tetramethylbutylphenol (Tinosorb M), bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S) and butyl methoxydibenzoylmethane as UVA absorbing filters, in the prevention of PLE under standardized photodiagnostic conditions. After determination of the minimal erythema dose at day 0, photoprovocation was performed in 12 patients with a clinical history of PLE, on days 1, 2 and 3 with 100 J/cm2 UVA and variable doses of UVB, starting with the 1.5-fold minimal erythema dose of UVB. Prior to irradiation, placebo was applied to the right and sunscreen to the left dorsal forearm under COLIPA (European Cosmetic, Toiletry and Perfumery Association) conditions. In 10 patients PLE could be provoked at the placebo site, with positive reactions in 90% of the UVA, 40% of the UVB and 90% of the UVA/UVB irradiated fields. At the site with the active treatment none of these patients developed PLE. These data demonstrate that a sunscreen with effective filters against UVA and UVB can successfully prevent the development of PLE. Further studies are needed to examine whether regular application of sunscreen under everyday conditions, especially in doses less than the tested COLIPA-norm, could be an equivalent alternative to UV-hardening therapy.
Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome
2008-09-04

Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 μg/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 ( sgk1 −/− ) and their wild-type littermates ( sgk1 +/+ ). Doxorubicin treatment resulted in heavy proteinuria (&gt;100 mg protein/mg crea) in 15/44 of sgk1 +/+ and 15/44 of sgk1 −/− mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1 +/+ mice. Urinary sodium excretion reached signficantly lower values in sgk1 +/+ mice (15 ± 5 μmol/mg crea) than in sgk1 −/− mice (35 ± 5 μmol/mg crea) and was associated with a significantly higher body weight gain in sgk1 +/+ compared with sgk1 −/− mice (+6.6 ± 0.7 vs. +4.1 ± 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1 −/− mice than in sgk1 +/+ mice leading to uremia and a reduced median survival in sgk1 −/− mice (29 vs. 40 days in sgk1 +/+ mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.
Charge Cluster-to-Alanine Scanning of UL128 for Fine Tuning of the Endothelial Cell Tropism of Human Cytomegalovirus
2008-09-04

ABSTRACT The viral genes UL128, UL130, and UL131A have been identified as major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV), with deletion of either gene causing a null phenotype. We hypothesized that a functional scanning of these genes by minor genetic modifications would allow for the generation of mutants with an intermediate phenotype. By combining charge cluster-to-alanine (CCTA) mutagenesis with markerless mutagenesis of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain, we analyzed UL128 in order to identify functional sites and hence enable targeted modulation of the EC tropism of HCMV. A total of nine mutations in eight charge clusters were tested. Three of the CCTA mutations severely reduced EC tropism, three were irrelevant, two had a weak effect on cell tropism, and one mutation in the most C-terminal cluster caused an intermediate phenotype. All of the highly effective mutations were located in a core region (amino acids 72 to 106) which appears to be particularly crucial for EC tropism. The intermediate effect of mutations in the C-terminal cluster could be modulated by varying the number of amino acids replaced with alanine. This study provides a rational approach for targeted modulation of HCMV cell tropism, which may aid in the development of HCMV strains with a desired degree of attenuation.
Running on uneven ground: leg adjustment to vertical steps and self-stability
2008-09-05

SUMMARY Human running is characterized by comparably simple whole-body dynamics. These dynamics can be modelled with a point mass bouncing on a spring leg. Theoretical studies using such spring–mass models predict that running can be self-stable. In simulations, this self-stability allows for running on uneven ground without paying attention to the ground irregularities. Whether humans actually use this property of the mechanical system in such an irregular environment is, however, unclear. One way to approach this question is to study how the leg stiffness in stance and the leg orientation in flight are changed in response to ground perturbations. Here, for 11 human subjects we studied two consecutive contacts during running on uneven ground with a force plate of adjustable height (step of +5, +10 and +15 cm). We found that runners adjust their leg stiffness to the height of a vertical step. The adjustment is characterized by a 9% increase in leg stiffness in preparation for the perturbation and by a systematic decrease in proportion to the step height. At the highest vertical step (+15 cm), leg stiffness was reduced by about 26%. We also observed that the angle of attack decreased from 68 deg. to 62 deg. with increasing ground height. These leg adjustments are in accordance with the predictions of a stable spring–mass system. Furthermore, we could describe the identified leg forces and leg compressions with a simple spring–mass simulation for a given body mass, leg stiffness, angle of attack and initial conditions. We compared the experimental findings with the self-stabilizing properties of the spring–mass model, and discuss how humans use a combination of strategies that include purely mechanical self-stabilization and active neuromuscular control. Finally, beyond self-stability, we suggest that control may apply to smooth centre of mass kinematics.
Hypoxia inducible factor‐1 (HIF‐l)‐mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium
2008-09-08

Diarrhea is widespread in intestinal diseases involving ischemia and/or hypoxia. Since hypoxia alters stimulated C P and water flux, we investigated the influence of such a physiologically and pathophysiologi‐cally important signal on expression of the cystic fibrosis transmembrane conductance regulator (CFTR). Located on the apical membrane, this cAMP‐activated C P channel determines salt and fluid transport across mucosal surfaces. Our studies revealed depression of CFTR mRNA, protein, and function in hypoxic epithe‐lia. Chromatin immunoprecipitation identified a previ‐ously unappreciated binding site for the hypoxia induc‐ible factor‐1 (HIF‐1), and promoter studies established its relevance by loss of repression following point mutation. Consequently, HIF‐1 overexpressing cells exhibited significantly reduced transport capacity in colorimetric C P efflux studies, altered short circuit measurements, and changes in transepithelial fluid movement. Whole‐body hypoxia in wild‐type mice re‐sulted in significantly reduced small intestinal fluid and HCO 3 ‐ secretory responses to forskolin. Experiments performed in Cftr ‐/‐ and Nkcc1 ‐/‐ mice underlined the role of altered CFTR expression for these functional changes, and work in conditional Hifla mutant mice verified HIF‐1‐dependent CFTR regulation in vivo. In summary, our study clarifies CFTR regulation and introduces the concept of a HIF‐1‐orchestrated response designed to regulate ion and fluid movement across hypoxic intestinal epithelia.—Zheng, W., Kuh‐licke, J., Jäckel, K., Eltzschig, H. K., Singh, A., Sjöblom, M., Riederer, B., Weinhold, C., Seidler, U., Colgan, S. P., Karhausen, J. Hypoxia inducible factor‐1 (HIF‐1) ‐mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithe‐lium. FASEB J. 23, 204‐213 (2009)
Visualizing wiki-supported knowledge building
2008-09-08

It is widely accepted that wikis are valuable tools for successful collaborative knowledge building. In this paper, we describe how processes of knowledge building with wikis may be visualized, citing Wikipedia as an example. The underlying theoretical basis of our paper is the framework for collaborative knowledge building with wikis, as introduced by Cress and Kimmerle [2], [3], [4]. This model describes collaborative knowledge building as a co-evolution of individual and collective knowledge, or of cognitive and social systems respectively. These co-evolutionary processes may be visualized graphically, applying methods from social network analysis, especially those methods that take dynamic changes into account [5], [18]. For this purpose, we have undertaken to analyze, on the one hand, the temporal development of an article in the German version of Wikipedia and related articles that are linked to this core article. On the other hand, we analyzed the temporal development of those users who worked on these articles. The resulting graphics show an analogous process, both with regard to the articles that refer to the core article and to the users involved. These results provide empirical support for the co-evolution model. Some implications of our findings and the potential for future research on collaborative knowledge building with wikis and on the application of social network analysis are discussed at the end of the article.
Effect of fluctuations on the superfluid-supersolid phase transition on the lattice
2008-09-08

We derive a controlled expansion into mean field plus fluctuations for the extended Bose-Hubbard model, involving interactions with many neighbors on an arbitrary periodic lattice, and study the superfluid-supersolid phase transition. Near the critical point, the impact of (thermal and quantum) fluctuations on top of the mean field grows, which entails striking effects, such as negative superfluid densities and thermodynamical instability of the superfluid phase-earlier as expected from mean-field dynamics. We also predict the existence of long-lived "supercooled" states with anomalously large quantum fluctuations.
Placental Malaria Increases Malaria Risk in the First 30 Months of Life
2008-09-09

Our findings show that active placental P. falciparum infection detected at delivery is associated with an approximately 2-fold greater risk of malaria during early life, compared with noninfection. The fact that persons born to infected multigravidae rather than primigravidae appear to be at greater risk emphasizes the importance of preventing malaria in mothers of all gravidities.
Adjuvant treatment with vindesine in comparison to observation alone in patients with metastasized melanoma after complete metastasectomy: a randomized multicenter trial of the German Dermatologic Cooperative Oncology Group
2008-09-09

To evaluate the efficacy and safety of vindesine in patients with metastatic melanoma after complete metastasectomy. One hundred and forty-two patients with metastatic spread to regional sites, lymph nodes, and distant sites after complete metastasectomy were randomized to receive either treatment with vindesine for 2 years or observation alone. Vindesine 3 mg/m intravenously was administered biweekly for the first 26 weeks following 3-week intervals for an additional 26 weeks and thereafter every 4 weeks for 52 weeks. One hundred and thirty-nine patients were eligible for intent-to-treat analysis. Median follow-up time was 46 months. Median recurrence free survival was 7.9 months in the vindesine group and 7.6 months in the observational group (P=0.40). Three-year overall survival rate was 54.9% (37 patients) for patients receiving vindesine in comparison to 43.6% (31 patients) in the observation arm (P=0.07). No grade IV toxicity was observed. The two major side effects in the vindesine group were alopecia and peripheral neuropathy. Ten patients went off treatment because of grade III toxicity. Adjuvant treatment with vindesine did not significantly prolong disease free or overall survival in high-risk melanoma patients. Thus, this randomized trial did not confirm earlier reports of beneficial effects of adjuvant vindesine and can therefore not be recommended.
Towards automatic software model checking of thousands of Linux modules—a case study with Avinux
2008-09-09

Abstract Modular software model checking of large real‐world systems is known to require extensive manual effort in environment modelling and preparing source code for model checking. Avinux is a tool chain that facilitates the automatic analysis of Linux and especially of Linux device drivers. The tool chain is implemented as a plugin for the Eclipse IDE, using the source code bounded model checker CBMC as its backend. Avinux supports a verification process for Linux that is built upon specification annotations with SLICx (an extension of the SLIC language), automatic data environment creation, source code transformation and simplification, and the invocation of the verification backend. In this paper technical details of the verification process are presented: Using Avinux on thousands of drivers from various Linux versions led to the discovery of six new errors. In these experiments, Avinux also reduced the immense overhead of manual code preprocessing that other projects incurred. Copyright © 2008 John Wiley &amp; Sons, Ltd.
HPMA as a Scaffold for the Modular Assembly of Functional Peptide Polymers by Native Chemical Ligation
2008-09-09

Synthetic peptides are valuable tools in fundamental and applied biomedical research. On one hand, these molecules provide highly efficient access to competitive inhibitors of molecular interactions and enzyme substrates by rational design. On the other hand, peptides may serve as powerful vectors to mediate cellular uptake of molecules that otherwise enter cells only poorly. The coupling of both such functionalities provides access to molecules interfering with molecular processes inside the cell. However, the combination of several functionalities on one synthetic peptide may be compromised by problems associated with the synthesis of long peptides. Native chemical ligation enables the chemoselective coupling of fully deprotected functional building blocks. However, peptide thioesters are still not accessible by standard solid-phase peptide synthesis. Here, we demonstrate the cofunctionalization of a thioester-activated N-hydroxypropyl methacrylamide (HPMA) copolymer (28,500 Da) with the cell-penetrating peptide (CPP) nonaarginine and a bioactive peptide as independent building blocks by native chemical ligation. Nonaarginine was employed as a cell-penetrating peptide (CPP), a fluorescein-labeled analogue of a pro-apoptotic peptide as a biofunctional cargo. Incorporation of the fluorescein label enabled the highly sensitive quantification of the coupling stoichiometry by fluorescence correlation spectroscopy (FCS) using 0.4 pmol/12 ng of labeled construct. A construct only bearing the functional cargo peptide required cellular import by electroporation in order to show activity. In contrast, a construct combining all functionalities was active upon incubation of cells, validating the modular nature of the approach.