julilili42/papers huggingface dataset:
The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation
2011-08-22

Abstract Although Candida glabrata is an important human pathogenic yeast, its pathogenicity mechanisms are largely unknown. Immune evasion strategies seem to play key roles during infection, since very little inflammation is observed in mouse models. Furthermore, C. glabrata multiplies intracellularly after engulfment by macrophages. In this study, we sought to identify the strategies that enable C. glabrata to survive phagosome biogenesis and antimicrobial activities within human monocyte-derived macrophages. We show that, despite significant intracellular proliferation, macrophage damage or apoptosis was not apparent, and production of reactive oxygen species was inhibited. Additionally, with the exception of GM-CSF, levels of pro- and anti-inflammatory cytokines were only marginally increased. We demonstrate that adhesion to and internalization by macrophages occur within minutes, and recruitment of endosomal early endosomal Ag 1 and lysosomal-associated membrane protein 1 indicates phagosome maturation. However, phagosomes containing viable C. glabrata, but not heat-killed yeasts, failed to recruit cathepsin D and were only weakly acidified. This inhibition of acidification did not require fungal viability, but it had a heat-sensitive surface attribute. Therefore, C. glabrata modifies the phagosome into a nonacidified environment and multiplies until the host cells finally lyse and release the fungi. Our results suggest persistence of C. glabrata within macrophages as a possible immune evasion strategy.
Negative Symptoms of Schizophrenia as Primary Target of Cognitive Behavioral Therapy: Results of the Randomized Clinical TONES Study
2011-08-22

Clinical studies on cognitive behavioral therapy (CBT) that include schizophrenia patients primarily on the basis of negative symptoms are uncommon. However, those studies are necessary to assess the efficacy of CBT on negative symptoms. This article first gives an overview of CBT on negative symptoms and discusses the methodological problems of selecting an adequate control group. Furthermore, the article describes a clinical study (the TONES-Study, ISRCTN 25455020), which aims to investigate whether CBT is specifically efficacious for the reduction of negative symptoms. This multicenter randomized clinical trial comparing CBT with cognitive remediation (CR) for control of nonspecific effects is depicted in detail. In our trial, schizophrenia patients (n = 198) participated in manualized individual outpatient treatments. Primary outcome is the negative syndrome assessed with the positive and negative syndrome scale, analyzed with multilevel linear mixed models. Patients in both groups moderately improved regarding the primary endpoint. However, against expectation, there was no difference between the groups after treatment in the intention to treat as well as in the per-protocol analysis. In conclusion, psychotherapeutic intervention may be useful for the reduction of negative symptoms. However, there is no indication for specific effects of CBT compared with CR.
Identification of a Potent and Selective Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist with Favorable Physicochemical and in Vitro ADME Properties
2011-08-22

The free fatty acid receptor 1 (FFA1, also known as GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and is recognized as an interesting new target for treatment of type 2 diabetes. Several series of selective FFA1 agonists are already known. Most of these are derived from free fatty acids (FFAs) or glitazones and are relatively lipophilic. Aiming for the development of potent, selective, and less lipophilic FFA1 agonists, the terminal phenyl of a known compound series was replaced by nitrogen containing heterocycles. This resulted in the identification of 37, a selective FFA1 agonist with potent activity on recombinant human FFA1 receptors and on the rat insulinoma cell line INS-1E, optimal lipophilicity, and excellent in vitro permeability and metabolic stability.
Trade Intermediation and the Organization of Exporters
2011-08-22

Abstract Empirical papers show that successful exporting firms either use unaffiliated foreign trade intermediaries or own foreign wholesale subsidiaries. However, conventional trade theory models assume that producers can directly access foreign consumers. We introduce intermediaries in an international trade model where producers differ with respect to productivity as well as regarding their varieties' perceived quality and tradability. Trade intermediation is prone to frictions owing to the absence of enforceable cross‐country contracts while own wholesale subsidiaries require additional capital investment. The sorting pattern of firms depends on their degree of competitive advantage; the equilibrium prevalence of intermediation in the industry depends negatively on the heterogeneity among producers, and the market‐specificity of goods, and positively on expropriation risk. Using sectoral US export data by destination country, we confirm the empirical validity of these predictions.
Glucose-Raising Genetic Variants in MADD and ADCY5 Impair Conversion of Proinsulin to Insulin
2011-08-22

By examining parameters of glucose-stimulated proinsulin-to-insulin conversion during an OGTT, we show that the SNP in ADCY5 is implicated in defective proinsulin-to-insulin conversion. In addition, we confirmed previous findings on the role of a genetic variant in MADD on proinsulin-to-insulin conversion. These effects may also be related to neighboring regions of the genome.
Shape, shear and flexion - II. Quantifying the flexion formalism for extended sources with the ray-bundle method★
2011-08-22

Flexion-based weak gravitational lensing analysis is proving to be a useful adjunct to traditional shear-based techniques. As flexion arises from gradients across an image, analytic and numerical techniques are required to investigate flexion predictions for extended image/source pairs. Using the Schwarzschild lens model, we demonstrate that the ray-bundle method for gravitational lensing can be used to accurately recover second flexion, and is consistent with recovery of zero first flexion. Using lens plane to source plane bundle propagation, we find that second flexion can be recovered with an error no worse than 1 per cent for bundle radii smaller than Δθ= 0.01θE and lens plane impact pararameters greater than θE+Δθ, where θE is the angular Einstein radius. Using source plane to lens plane bundle propagation, we demonstrate the existence of a preferred flexion zone. For images at radii closer to the lens than the inner boundary of this zone, indicative of the true strong lensing regime, the flexion formalism should be used with caution (errors greater than 5 per cent for extended image/source pairs). We also define a shear-zone boundary, beyond which image shapes are essentially indistinguishable from ellipses (1 per cent error in ellipticity). While suggestive that a traditional weak lensing analysis is satisfactory beyond this boundary, a potentially detectable non-zero flexion signal remains.
Optical requirements on magnification systems for intracranial video microsurgery
2011-08-22

From an optical point of view current operating microscopes meet the requirements of intracranial microneurosurgery. However, ergonomically further developments are highly desirable. Video microsurgery is a promising field and could hold a solution to this problem.
Structural investigations of a novel bacterial AB5toxin
2011-08-22

Treatment of hospital-acquired Staphylococcus infections remains a challenge as the number of strains with multiple antibiotic resistances has increased steadily over the last decades.This emphasizes the need for a new class of antibiotics that act on new targets.The major autolysins AtlE and AtlA of S. epidermidis and S. aureus, respectively, represent such targets.Both enzymes take over pivotal roles in cell division where they are responsible for the separation of daughter cells.The high-resolution structure of AmiE reveals for the first time detailed insights into the enzymatic function of a staphylococcal peptidoglycan (PGN) hydrolase and thereby provides the basis for the formulation of a likely mechanism of catalysis [1].With the synthesis of PGN fluorescent substrates, a method was established that offers the option to produce substrates of defined length and high purity [1,2].Easy modifiability of the synthetic substrates also allows probing the influence of amino acid substitutions on substrate recognition.It could be demonstrated that the presence of a third amino acid in the peptide stem as well as the isoform of glutamine in the second position are key motifs and essential for recognition by AmiE.These findings could also be confirmed in a docking model.Structural comparisons with other proteins sharing the amidase-fold reveal common features in the substrate grooves, which points to an evolutionary conserved mechanism of PGN recognition.Contrary to previous assumptions according to which the cell wall binding region (CBR) of the AtlE amidase contains only two repeat domains, the crystal structure of R 3,4 reveals the presence of four highly similar domains that belong to the family of SH3b domains.The sequence and structural similarity between every second repeat in the CBR is higher than between adjacent ones.A distinct patch of conserved residues could be located on opposite sides of each repeat in the R 3,4 tandem repeat.These areas might serve as binding pockets for negatively charged ligands such as teichoic acids.We are currently examining this possibility.Small angle x-ray scattering (SAXS) experiments of AmiE-R 1-4 and R 1-4 reveal that the hinge region between the catalytic domain and the first repeat module is more flexible than the second one separating R 1,2 from R 3,4 .In conjunction with the available structural data, it is now possible to draw a plausible mechanism of cell wall interaction in which the flexibility of the first linker ensures access of the catalytic domain to several PGN cleavage sites.The second linker serves to separate the two tandem repeats of the CBR.This creates a binding groove in R 3 that can easily be modulated by movement of the RT-loop.In comparison to its counterpart in R 4 , the RT-loop of R 3 is not engaged in any contacts with the preceding domain.
Cyclophosphamide for large vessel vasculitis: assessment of response by PET/CT.
2011-08-23

Pulse cyclophosphamide is effective in patients with large vessel vasculitis resistant to glucocorticosteroids. The high rate of sustained response in our patients suggests that treatment decisions based on clinical parameters combined with PET/CT may have a beneficial effect on the clinical outcome.
What are the main research findings during the last 5 years that have changed my approach to clinical practice?
2011-08-24

When asked to address the above question, findings that appeared to be among the most relevant included (1) interventions in the delivery room directed at supporting the physiological transition from intrauterine to extrauterine life rather than actively intervening in it; (2) recent data suggesting that keeping extremely low-gestational age neonates at a pulse oximeter saturation (SpO 2 ) of 91–95% would increase their chances of survival compared with aiming for lower SpO 2 values; (3) using caffeine citrate in infants &lt;1250 g with apnoea of prematurity improves neurodevelopmental outcome; (4) injecting antivascular epithelial growth factor into the vitreous seems to be an effective treatment for retinopathy of prematurity and (5) moderate hypothermia for perinatal hypoxic-ischaemic encephalopathy increases the likelihood of survival without neurological impairment. Here, data that support these recent changes in approach will be presented and discussed.
Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+exchanger NHE3 by glucocorticoids
2011-08-25

Na + /H + exchanger 3 (NHE3) is the major Na + transporter in the intestine. Serum- and glucocorticoid-induced kinase (SGK) 1 interacts with NHE regulatory factor 2 (NHERF2) and mediates activation of NHE3 by dexamethasone (Dex) in cultured epithelial cells. In this study, we compared short-term regulation of NHE3 by Dex in SGK1-null and NHERF2-null mice. In comparison to wild-type mice, loss of SGK1 or NHERF2 significantly attenuated regulation of NHE3 by Dex but did not completely obliterate the effect. We show that transfection of SGK2 or SGK3 in PS120 cells resulted in robust activation of NHE3 by Dex. However, unlike SGK1 or SGK2, SGK3 rapidly activated NHE3 within 15 min of Dex treatment in both PS120 and Caco-2bbe cells. Immunofluorescence analysis showed that SGK3 colocalized with NHE3 in recycling endosomes, whereas SGK1 and SGK2 were diffusely distributed. Mutation of Arg-90 of SGK3 disrupted the endosomal localization of SGK3 and delayed NHE3 activation. Activation of SGK3 and NHE3 by Dex was dependent on phosphoinositide 3-kinase (PI3K) and phosphoinositide-dependent kinase 1 (PDK1), and Dex induced translocation of PDK1 to endosomes. Our study identifies SGK3 as a novel endosomal kinase that acutely regulates NHE3 in a PI3K-dependent mechanism.
Lip and tongue movements during phonetic sequences: analysis and definition of normal values
2011-08-25

Precise knowledge of lip and tongue movements is limited. Conventional investigative methods do not allow for their precise representation and analysis. In the present study, electromagnetic articulography (EMA) was used to define normal values for lip movements based on consonant-vowel-consonant (CVC) sequences and for tongue movements based on vowel-consonant-vowel (VCV) sequences. The study population included 25 volunteers (11 males and 14 females) with a median age of 26 (23 to 29) years. An EMA unit was used to conduct the measurements. For this purpose, the volunteers repeated a number of VCV and CVC text sequences 10 times each during two different body positions (upright and relaxed). Statistical analysis (including Bland and Altman's measurement error, non-parametric Wilcoxon rank score testing, and analysis of variance) of distance and time variables resulted in a small measurement error. There was no effect of different body positions on measurement error. Gender was found to have a significant effect on the values measured (67 versus 17 per cent of variables related to distances in CVC versus VCV sequences and 38 versus 75 per cent of variables related to intervals in CVC versus VCV sequences). This finding did not, however, hold true for any of the other parameters investigated as potential influencing factors. EMA is capable of providing valuable information about lip and tongue movements and any pathological dysfunctions involved.
A Cluster Reduction for Computing the Subtree Distance Between Phylogenies
2011-08-26

Calculating the rooted subtree prune and regraft (rSPR) distance between two rooted binary phylogenetic trees is a frequently applied process in various areas of molecular evolution. However, computing this distance is an NP-hard problem and practical algorithms for computing it exactly are rare. In this paper, a divide-and-conquer approach to calculating the rSPR distance is established. This approach breaks the problem instance into a number of smaller and more tractable subproblems. Two reduction rules which were previously used to show that computing the rSPR distance is fixed-parameter tractable can easily be used to complement this new theoretical result, and so a significant positive impact on the running time of calculating this distance in practice is likely.
Coupling of Microphase Separation and Dewetting in Weakly Segregated Diblock Co-polymer Ultrathin Films
2011-08-26

We have studied the coupling behavior of microphase separation and autophobic dewetting in weakly segregated poly(ε-caprolactone)-block-poly(L-lactide) (PCL-b-PLLA) diblock co-polymer ultrathin films on carbon-coated mica substrates. At temperatures higher than the melting point of the PLLA block, the co-polymer forms a lamellar structure in bulk with a long period of L ∼ 20 nm, as determined using small-angle X-ray scattering. The relaxation procedure of ultrathin films with an initial film thickness of h = 10 nm during annealing has been followed by atomic force microscopy (AFM). In the experimental temperature range (100-140 °C), the co-polymer dewets to an ultrathin film of itself at about 5 nm because of the strong attraction of both blocks with the substrate. Moreover, the dewetting velocity increases with decreasing annealing temperatures. This novel dewetting kinetics can be explained by a competition effect of the composition fluctuation driven by the microphase separation with the dominated dewetting process during the early stage of the annealing process. While dewetting dominates the relaxation procedure and leads to the rupture of the ultrathin films, the composition fluctuation induced by the microphase separation attempts to stabilize them because of the matching of h to the long period (h ∼ 1/2L). The temperature dependence of these two processes leads to this novel relaxation kinetics of co-polymer thin films.
Stem Cell Factor Plasma Levels are Decreased in Alzheimer's Disease Patients with Fast Cognitive Decline after One-Year Follow-Up Period: The Pythia-Study
2011-08-26

Alzheimer's disease (AD) is the most common cause of cognitive decline in the elderly and is characterized by massive neuronal loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. Decreased SCF plasma levels have been described in AD patients. Whether SCF plasma levels are also associated with the rate of cognitive decline in AD patients has not been reported so far. In the present study, we demonstrate that SCF plasma levels are significantly decreased in AD patients with fast cognitive decline (decrease of Mini-Mental State Examination [MMSE] score > 4 after one year; n = 12) compared to AD patients with slow cognitive decline (decrease of MMSE score ≤ 4 after one year; n = 28) (fast versus slow cognitive decline: mean ± SD: 1051.1 ± 178.7 versus 1237.9 ± 274.2 pg/ml; p = 0.037). Moreover, SCF plasma levels correlated with the rate of cognitive decline after one year follow-up period (r = 0.315; p = 0.048). In a multiple linear regression analysis, independent predictors of the rate of cognitive decline in our study cohort were age, MMSE scores at baseline, SCF plasma levels, as well as brain-derived neurotrophic factor and activated glycoprotein (GP) IIb/IIIa. These results suggest that lower SCF plasma levels are associated with a higher rate of cognitive decline in AD patients. Thus, treatment strategies increasing SCF plasma levels could be useful for delaying the progression of AD. Further prospective studies are needed to elucidate the value of plasma SCF in a multimarker approach determining AD prognosis.
6-(4-Methoxyphenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-carbaldehyde
2011-08-26

The 4-methoxyphenyl residue in the title compound, C21H19NO2, is oriented at a dihedral angle of 54.6&amp;#8197;(5)&amp;#176; with respect to the phenyl ring and at a dihedral angle of 52.5&amp;#8197;(8)&amp;#176; with respect to the pyrrole ring of the pyrrolizine system. The phenyl ring is oriented at a dihedral angle of 36.2&amp;#8197;(5)&amp;#176; with respect to the pyrrole ring. The methoxy group makes a C&amp;#8212;C&amp;#8212;O&amp;#8212;C torsion angle of 3.8&amp;#8197;(9)&amp;#176; with the attached benzene ring.
BRI2 Protein Regulates β-Amyloid Degradation by Increasing Levels of Secreted Insulin-degrading Enzyme (IDE)
2011-08-27

The amyloid precursor protein (APP) is one of the major proteins involved in Alzheimer disease (AD). Proteolytic cleavage of APP gives rise to amyloid-β (Aβ) peptides that aggregate and deposit extensively in the brain of AD patients. Although the increase in levels of aberrantly folded Aβ peptide is considered to be important to disease pathogenesis, the regulation of APP processing and Aβ metabolism is not fully understood. Recently, the British precursor protein (BRI2, ITM2B) has been implicated in influencing APP processing in cells and Aβ deposition in vivo. Here, we show that the wild type BRI2 protein reduces plaque load in an AD mouse model, similar to its disease-associated mutant form, ADan precursor protein (ADanPP), and analyze in more detail the mechanism of how BRI2 and ADanPP influence APP processing and Aβ metabolism. We find that overexpression of either BRI2 or ADanPP reduces extracellular Aβ by increasing levels of secreted insulin-degrading enzyme (IDE), a major Aβ-degrading protease. This effect is also observed with BRI2 lacking its C-terminal 23-amino acid peptide sequence. Our results suggest that BRI2 might act as a receptor protein that regulates IDE levels that in turn influences APP metabolism in a previously unrecognized way. Targeting the regulation of IDE may be a promising therapeutic approach to sporadic AD.
Proceedings of the ACM SIGGRAPH Symposium on Applied Perception in Graphics and Visualization
2011-08-27

Welcome to APGV 2011! We are pleased to present you the proceedings of the eighth annual Symposium on Applied Perception in Graphics and Visualization, held in Toulouse, France, August 27-28, 2011. The symposium aims at, on the one hand, using insights from perception to advance the field of visual, auditory and multi-sensory representation while, on the other hand, using computer graphics to enable research on perceptual issues that may otherwise not be possible. APGV has traditionally fostered interaction between the fields of perception, graphics and visualization. This year, we have emphasized this tradition by co-locating the symposium with the 34th European Conference on Visual Perception (ECVP). We hope to create synergies between the two research communities, which obviously share a lot of common interests. We received a total of 33 paper submissions. Each submission received three reviews, either by members of the International Program Committee, or external reviewers carefully chosen by them. From those reviews and some additional discussions, 19 papers were finally selected for oral presentation at the conference. Veronica Sundstedt, this year's Posters Chair, additionally selected 17 submissions, highlighting late-breaking research in the field. Following the current arrangement with ACM Transactions on Applied Perception (TAP), five submissions underwent a second review cycle for inclusion in the APGV special issue of the ACM TAP journal. These five submissions were selected by the Program Chairs, based on comments and recommendations made in the reviews. To grant publication, the authors were asked to address all the comments in the summary review; most of them actually went the extra mile and spent additional time and effort to provide the best possible papers. These papers will appear in the ACM Digital Library as TAP papers at the same time as the symposium takes place. They cannot appear in the APGV proceedings in order to avoid double publication. In addition to the reviewed papers and posters, and as an immediate outcome of the APGV-ECVP collaboration, this year we are honored to have an impressive list of invited speakers, organized in two short joint symposia on Sunday. The first symposium, organized by Quasim Zaidi and Martin Giese, is entitled 'Deforming shapes - deformable templates' and the second one, organized by Simon Thorpe, is entitled 'Computer Vision & Biological Vision'. Furthermore, all APGV attendees are kindly invited to attend ECVP's Rank Price plenary lecture by Stan Dehaene: 'How learning to read changes the visual system'.