julilili42/papers huggingface dataset:
Treating gravity in thin-disk simulations
2012-03-13

In 2D simulations of thin gaseous disks with embedded planets or self-gravity the gravitational potential needs to be smoothed to avoid singularities in the numerical evaluation of the gravitational potential or force. In order to correctly resemble the realistic case of vertically extended 3D disks the softening prescription used in 2D needs to be adjusted properly. In this paper we analyze the embedded planet and the self-gravity case and provide a method to evaluate the required smoothing in 2D simulations of thin disks. Starting from the averaged hydrodynamic equations and using a vertically isothermal disk model, we calculate the force. We compare our results to the often used Plummer form of the potential which runs as \\propto 1/(r^2+\\epsilon^2)^{1/2}. For that purpose we compute the required smoothing length \\epsilon as a function of distance r to the planet or to a disk element within a self-gravitating disk. We find that for larger distances \\epsilon is determined solely by the vertical disk thickness H. For the planet case we find that outside r\\simH a value of \\epsilon = 0.7H describes the averaged force very well, while in the self-gravitating disk the value needs to be larger, \\epsilon = 1.2H. For smaller distances the smoothing needs to be reduced significantly. Comparing torque densities of 3D and 2D simulations we show that the modification to the vertical density stratification as induced by an embedded planet needs to be taken into account to obtain agreeing results. In disk fragmentation simulations the choice of \\epsilon can determine whether a disk will fragment or not. Because a wrong smoothing length can change even the direction of migration, it is very important to include the effect of the planet on the local scale height in 2D planet-disk simulations. We provide an approximate and fast method for this purpose which gives very good agreement to full 3D simulations.
Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity
2012-03-13

Synaptic long-term potentiation (LTP) at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes. Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear. Here, we found that Protein Kinase G1 (PKG-I) localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP. Using the Cre-lox P system, we generated nociceptor-specific knockout mice lacking PKG-I specifically in presynaptic terminals of nociceptors in the spinal cord, but not in post-synaptic neurons or elsewhere (SNS-PKG-I(-/-) mice). Patch clamp recordings showed that activity-induced LTP at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) was completely abolished in SNS-PKG-I(-/-) mice, although basal synaptic transmission was not affected. Analyses of synaptic failure rates and paired-pulse ratios indicated a role for presynaptic PKG-I in regulating the probability of neurotransmitter release. Inositol 1,4,5-triphosphate receptor 1 and myosin light chain kinase were recruited as key phosphorylation targets of presynaptic PKG-I in nociceptive neurons. Finally, behavioural analyses in vivo showed marked defects in SNS-PKG-I(-/-) mice in several models of activity-induced nociceptive hypersensitivity, and pharmacological studies identified a clear contribution of PKG-I expressed in spinal terminals of nociceptors. Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are operational in the expression of synaptic LTP on spinal-PAG projection neurons and that PKG-I localized in presynaptic nociceptor terminals plays an essential role in this process to regulate pain sensitivity.
Complete Mitochondrial Genomes Reveal Neolithic Expansion into Europe
2012-03-13

The Neolithic transition from hunting and gathering to farming and cattle breeding marks one of the most drastic cultural changes in European prehistory. Short stretches of ancient mitochondrial DNA (mtDNA) from skeletons of pre-Neolithic hunter-gatherers as well as early Neolithic farmers support the demic diffusion model where a migration of early farmers from the Near East and a replacement of pre-Neolithic hunter-gatherers are largely responsible for cultural innovation and changes in subsistence strategies during the Neolithic revolution in Europe. In order to test if a signal of population expansion is still present in modern European mitochondrial DNA, we analyzed a comprehensive dataset of 1,151 complete mtDNAs from present-day Europeans. Relying upon ancient DNA data from previous investigations, we identified mtDNA haplogroups that are typical for early farmers and hunter-gatherers, namely H and U respectively. Bayesian skyline coalescence estimates were then used on subsets of complete mtDNAs from modern populations to look for signals of past population expansions. Our analyses revealed a population expansion between 15,000 and 10,000 years before present (YBP) in mtDNAs typical for hunters and gatherers, with a decline between 10,000 and 5,000 YBP. These corresponded to an analogous population increase approximately 9,000 YBP for mtDNAs typical of early farmers. The observed changes over time suggest that the spread of agriculture in Europe involved the expansion of farming populations into Europe followed by the eventual assimilation of resident hunter-gatherers. Our data show that contemporary mtDNA datasets can be used to study ancient population history if only limited ancient genetic data is available.
Bet‐hedging germination in annual plants: a sound empirical test of the theoretical foundations
2012-03-13

Seed dormancy is thought to be a key mechanism allowing annual plants to spread extinction risk in unpredictably varying environments. Theory predicts increasing germination fractions with increasing probability of reproductive success but solid empirical evidence is scarce and often confounded with environmental factors. Here we provide an empirical test of bet‐hedging via delayed germination for three annual plant species along a ‘predictability gradient’ in Israel. We excluded confounding environmental and maternal effects by raising inbred seed families and germinating them under controlled conditions. Additionally, we germinated field‐collected seeds in three consecutive seasons to compare their germination with inbred families where maternal effects were removed. Risk of reproductive failure was quantified using demographic data from the field and from second‐generation inbred lines raised in a rainfall gradient in the greenhouse. Our findings were consistent with bet‐hedging theory in that germination fraction was negatively related to species‐ and site‐specific risk of reproductive failure. Both field and hand‐raised seeds of one species exhibited higher dormancy with increasing risk of reproductive failure across sites, and hand‐raised seeds of another species showed the same pattern. The third species exhibited a rather random pattern of germination between years and sites, corresponding to the lack of site‐specific risk of reproductive failure. Species‐specific patterns of dormancy and risk could be related to alternative risk‐spreading strategies such as high adult survival, but were also affected by phylogeny. We provide strong empirical evidence for seed dormancy being a mechanism to reduce the risk of reproductive failure in highly variable environments, but a larger number of rigorous experimental tests of bet hedging germination are needed. Specifically, the genetic basis of bet‐hedging must be shown in species with different life histories, for demonstrating that dormancy is adaptive and how it is modified by other risk‐spreading traits.
Multifunctional Profiling of Non–Small Cell Lung Cancer Using 18F-FDG PET/CT and Volume Perfusion CT
2012-03-13

(18)F-FDG uptake correlates with Ki67, whereas BF, BV, and K(trans) correlate with MVD. Therefore, (18)F-FDG uptake and perfusion parameters provide complementary functional information. An improved tumor profiling will be beneficial for both prognosis and therapy response evaluation in these tumors.
POWER LAWS AND OTHER HEAVY-TAILED DISTRIBUTIONS IN LINGUISTIC TYPOLOGY
2012-03-13

The paper investigates the quantitative distribution of language types across languages of the world. The studies are based on three large-scale typological data bases: The World Color Survey, the Automated Similarity Judgment Project data base, and the World Atlas of Language Structures. The main finding is that a surprisingly large and varied collection of linguistic typologies show power law behavior. The bulk of the paper deals with the statistical validation of these findings.
Recruitment of Natural Killer Cells in Advanced Stages of Endogenously Arising B-cell Lymphoma
2012-03-13

During inflammation and in transplantable tumor models, natural killer (NK) cells are recruited to pathologic tissues and activated to produce proinflammatory cytokines favoring adaptive immune responses of the T-helper type 1 (Th1) type. Interferon (IFN)-γ is needed to induce chemokines that attract NK cells in transplanted tumors. Nothing, however, is known on NK-cell migration in spontaneous tumors. As effective recruitment is a prerequisite for therapeutic NK-cell transfer, we investigated the cytokine milieu and the mechanisms that are instrumental for NK-cell accumulation in an endogenous tumor model. We make use of λ-myc transgenic mice that harbor the c-myc oncogene and develop spontaneous B-cell lymphoma. In contrast to lymphomas induced by tumor cell injection, virtually no IFN-γ produced by NK or by other cells was present in the tumor environment, particularly in advanced stages. Dendritic cells showed an impaired expression of interleukin-12, which is suggestive of deficient Th1 priming. The IFN-γ-dependent chemokines CXCL9 and CXCL10 were pivotal for NK-cell migration in the endogenous lymphoma model. Although IFN-γ was absent in late tumor stages, there was still expression of CXCL9 and CXCL10 with an ongoing influx of NK cells. The results demonstrate that transplantable tumor models do not reflect the situation as found in endogenously arising neoplasia, because in the latter, effective Th1 and cytotoxic T-lymphocyte responses are presumably not induced because of impaired IFN-γ production. The data also suggest that CXCL9 and CXCL10 production and NK-cell migration become independent of IFN-γ during tumor progression, and therefore support approaches of adoptive NK-cell transfer that hold promise for treatment of cancer.
Toward the Quantum Chemical Calculation of NMR Chemical Shifts of Proteins. 2. Level of Theory, Basis Set, and Solvents Model Dependence
2012-03-14

It has been demonstrated that the fragmentation scheme of our adjustable density matrix assembler (ADMA) approach for the quantum chemical calculations of very large systems is well-suited to calculate NMR chemical shifts of proteins [ Frank et al. Proteins2011, 79, 2189-2202 ]. The systematic investigation performed here on the influences of the level of theory, basis set size, inclusion or exclusion of an implicit solvent model, and the use of partial charges to describe additional parts of the macromolecule on the accuracy of NMR chemical shifts demonstrates that using a valence triple-ζ basis set leads to large improvement compared to the results given in the previous publication. Additionally, moving from the B3LYP to the mPW1PW91 density functional and including partial charges and implicit solvents gave the best results with mean absolute errors of 0.44 ppm for hydrogen atoms excluding H(N) atoms and between 1.53 and 3.44 ppm for carbon atoms depending on the size and also on the accuracy of the protein structure. Polar hydrogen and nitrogen atoms are more difficult to predict. For the first, explicit hydrogen bonds to the solvents need to be included and, for the latter, going beyond DFT to post-Hartree-Fock methods like MP2 is probably required. Even if empirical methods like SHIFTX+ show similar performance, our calculations give for the first time very reliable chemical shifts that can also be used for complexes of proteins with small-molecule ligands or DNA/RNA. Therefore, taking advantage of its ab initio nature, our approach opens new fields of application that would otherwise be largely inaccessible due to insufficient availability of data for empirical parametrization.
Epidemiology of malaria and helminth interaction
2012-03-14

Hookworm, A. lumbricoides and Schistosoma species were found to associate differently with malaria, which might explain the conflicting reports on interaction between helminths and malaria. It is therefore important to further investigate these three major helminths in relation to malaria, using universally accepted 'gold standard' study designs, which would be able to clearly define the nature of the interaction between malaria and helminth species. A better understanding of helminths and malaria coinfection may strengthen malaria control programmes in coendemic areas.
Enabling global processing in simultanagnosia by psychophysical biasing of visual pathways
2012-03-14

A fundamental aspect of visual cognition is our disposition to see the 'forest before the trees'. However, damage to the posterior parietal cortex, a critical brain region along the dorsal visual pathway, can produce a neurological disorder called simultanagnosia, characterized by a debilitating inability to perceive the 'forest' but not the 'trees' (i.e. impaired global processing despite intact local processing). This impairment in perceiving the global shape persists even though the ventral visual pathway, the primary recognition pathway, is intact in these patients. Here, we enabled global processing in patients with simultanagnosia using a psychophysical technique, which allowed us to bias stimuli such that they are processed predominantly by the intact ventral visual pathway. Our findings reveal that the impairment in global processing that characterizes simultanagnosia stems from a disruption in the processing of low-spatial frequencies through the dorsal pathway. These findings advance our understanding of the relationship between visuospatial attention and perception and reveal the neural mechanism mediating the disposition to see the 'forest before the trees'.
Overactive bladder symptoms and voiding dysfunction in neurologically normal women
2012-03-14

Abstract Aims To understand mechanisms underlying overactive bladder (OAB) and voiding dysfunction (VD) in neurologically normal women. Methods Review of MEDLINE from (1982) to (2011) using defined search terms, and manual analysis. Only articles published in English were included. Results One in five women report moderate to severe lower urinary tract symptoms (LUTS). Whilst VD is more common in men, women report a higher rate of storage symptoms or post‐micturition symptoms. Post‐void residual (PVR) volume measurements are vital in the assessment of women with LUTS and patients with VD without stress incontinence (SUI) are likely to have an elevated PVR (82%). Bladder outlet obstruction (BOO) also causes VD in women and can be alleviated by surgery or alpha‐blocker therapy, although OAB symptoms typically remain. Surgical repair for SUI can result in temporary VD in the minority of patients, highlighting the complex interplay that is emerging in the urethral bladder functioning complex in women. Conclusions Women with impaired bladder emptying present with a wide range of LUTS, and PVR measurement is essential for diagnosis. OAB and VD can clearly coexist and accurate diagnosis of underlying pathophysiology is required. Recommendations for clinical practice and research are provided including: investigation of VD in women with OAB; evaluation of PVR values to determine appropriate therapy and identification of BOO. There is clearly a need for further research into the impact of alpha‐blockers in women with VD as well as an evaluation of PVR changes in women with OAB before and after antimuscarinic therapy. Neurourol. Urodynam. 31:422–428, 2012. © 2012 Wiley Periodicals, Inc.
Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database
2012-03-15

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.
Integration Parliaments in Europe and Latin America: Explaining Variations
2012-03-15

In the past decades, European efforts to build a strong supranational organization have been successful in many ways. Among other accomplishments, Europeans have implemented a monetary union and a supranational decision-making system. While in the "Old Continent" progresses in integration are often the target of criticism by both pro- and anti-Europe groups, on the other side of the Atlantic policymakers look at the European Union (EU) as an uncontested example of achievement. Since the first attempts to translate Latin American integration projects into institutions, the design of the EU has been more than a reference, serving as a source for institutional imitation.
Predictive value and reward in implicit classification learning
2012-03-15

Abstract Learning efficacy depends on its emotional context. The contents learned and the feedback received during training tinges this context. The objective here was to investigate the influence of content and feedback on the efficacy of implicit learning and to explore using functional imaging how these factors are processed in the brain. Twenty‐one participants completed 150 trials of a probabilistic classification task (predicting sun or rain based on combinations of playing cards). Smileys or frowneys were presented as feedback. In 10 of these subjects, the task was performed during functional magnetic resonance imaging. Card combinations predicting sun were remembered better than those predicting rain. Similarly, positive feedback fortified learning more than negative feedback. The presentation of smileys recruited bilateral nucleus accumbens, sensorimotor cortex, and posterior cingulum more than negative feedback did. The higher the predictive value of a card combination, the more activation was found in the lateral cerebellum. Both context and feedback influence implicit classification learning. Similar to motor skill acquisition, positive feedback during classification learning is processed in part within the sensorimotor cortex, potentially reflecting the activation of a dopaminergic projection to motor cortex (Hosp et al., 2011). Activation of the lateral cerebellum during learning of combinations with high predictive value may reflect the formation of an internal model. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Green Fluorescent Protein (GFP) Color Reporter Gene Visualizes Parvovirus B19 Non-Structural Segment 1 (NS1) Transfected Endothelial Modification
2012-03-15

BACKGROUND: Human Parvovirus B19 (PVB19) has been associated with myocarditis putative due to endothelial infection. Whether PVB19 infects endothelial cells and causes a modification of endothelial function and inflammation and, thus, disturbance of microcirculation has not been elucidated and could not be visualized so far. METHODS AND FINDINGS: To examine the PVB19-induced endothelial modification, we used green fluorescent protein (GFP) color reporter gene in the non-structural segment 1 (NS1) of PVB19. NS1-GFP-PVB19 or GFP plasmid as control were transfected in an endothelial-like cell line (ECV304). The endothelial surface expression of intercellular-adhesion molecule-1 (CD54/ICAM-1) and extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) were evaluated by flow cytometry after NS-1-GFP or control-GFP transfection. To evaluate platelet adhesion on NS-1 transfected ECs, we performed a dynamic adhesion assay (flow chamber). NS-1 transfection causes endothelial activation and enhanced expression of ICAM-1 (CD54: mean ± standard deviation: NS1-GFP vs. control-GFP: 85.3 ± 11.2 vs. 61.6 ± 8.1; P<0.05) and induces endothelial expression of EMMPRIN/CD147 (CD147: mean ± SEM: NS1-GFP vs. control-GFP: 114 ± 15.3 vs. 80 ± 0.91; P<0.05) compared to control-GFP transfected cells. Dynamic adhesion assays showed that adhesion of platelets is significantly enhanced on NS1 transfected ECs when compared to control-GFP (P<0.05). The transfection of ECs was verified simultaneously through flow cytometry, immunofluorescence microscopy and polymerase chain reaction (PCR) analysis. CONCLUSIONS: GFP color reporter gene shows transfection of ECs and may help to visualize NS1-PVB19 induced endothelial activation and platelet adhesion as well as an enhanced monocyte adhesion directly, providing in vitro evidence of possible microcirculatory dysfunction in PVB19-induced myocarditis and, thus, myocardial tissue damage.