julilili42/papers huggingface dataset:
International competition with non-linear pricing
2013-03-01

This paper models international competition between two upstream firms, one domestic and one foreign, which both serve a domestic downstream firm. The productivity of their inputs in downstream production is private information of the downstream firm. We scrutinize the optimal non-linear pricing schemes and compare them to linear pricing. In particular, we show that a reduction in trade costs does not reduce domestic input demand if upstream firms compete with non-linear pricing schemes, contrary to the effects of trade liberalization when pricing has to be linear. JEL-Classification: F12, D43
Budgeting as informed guess work: Has the german budgetary process lost direction?
2013-03-01

Budgeting in Germany is characterized by procedural continuities which have developed more and more into dignified parts of the German financial constitution. This is true for the way budgets are prepared at the executive level, controlled in parliament and audited. Procedural accuracies do, however, mean little for budgetary outcomes. Typical for these is that hard choices tend to be avoided by the frequent use of off-budget funds, and that, so far, mere lip-service has been paid to the problem of reducing the deficit. Budgetary compromises necessary to reconcile cut-back rhetoric and ever-growing expenditure demands have become more complicated because in most cases the support reform of entitlements. By adding huge new
Biological and Tumor-Promoting Effects of Dioxin-like and Non-Dioxin-like Polychlorinated Biphenyls in Mouse Liver After Single or Combined Treatment
2013-03-02

To assess the impact of a mixture containing dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs), male mice were initiated with N-nitroso-diethylamine and subsequently treated with PCB126, an Ah-Receptor agonist, and PCB153, acting via activation of the constitutive androstane receptor. The two congeners were given at two dose levels: the low dose was adjusted to induce ~150-fold increases in cytochrome P450 (Cyp)1a1 (PCB126) and Cyp2b10 mRNAs (PCB153), and the high dose was chosen as twice the low dose. To keep the liver PCB levels constant, mice were given initial loading doses followed by weekly maintenance doses calculated on the basis of the PCBs' half-lives. Mice were treated with the individual congeners (low and high dose) or with a mixture consisting of the low doses of the 2 PCBs. The following results were obtained: (1) the 2 PCBs produced dose-dependent increases in Cyp1a1 and Cyp2b10 mRNA, protein, and activity when given individually; (2) combined treatment caused more than additive effects on Cyp1a1 mRNA expression, protein level, and ethoxyresurofin activity; (3) changes in the levels of several proteins were detected by proteome analysis in livers of PCB-treated mice; (4) besides these biological responses, the individual PCBs caused no significant increase in the number of glucose-6-phospatase (G6Pase)-deficient neoplastic lesions in liver, whereas a moderate significant effect occurred in the combination group. These results suggest weak but significant response-additive effects of the 2 PCBs when given in combination. They also suggest that the Cyp biomarkers tend to overestimate the carcinogenic response produced by the PCBs in mouse liver.
The microtubule‐associated kinase‐like protein RUNKEL functions in somatic and syncytial cytokinesis
2013-03-02

Summary The microtubule ( MT )‐associated putative kinase RUNKEL ( RUK ) is an important component of the phragmoplast machinery involved in cell plate formation in A rabidopsis somatic cytokinesis. Since loss‐of‐function ruk mutants display seedling lethality, it was previously not known whether RUK functions in mature sporophytes or during gametophyte development. In this study we utilized RUK proteins that lack the N ‐terminal kinase domain to further examine biological processes related to RUK function. Truncated RUK proteins when expressed in wild‐type A rabidopsis plants cause cellularization defects not only in seedlings and adult tissues but also during male meiocyte development, resulting in abnormal pollen and reduced fertility. Ultrastructural analysis of male tetrads revealed irregular and incomplete or absent intersporal cell walls, caused by disorganized radial MT arrays. Moreover, in ruk mutants endosperm cellularization defects were also caused by disorganized radial MT arrays. Intriguingly, in seedlings expressing truncated RUK proteins, the kinesin HINKEL , which is required for the activation of a mitogen‐activated protein kinase signaling pathway regulating phragmoplast expansion, was mislocalized. Together, these observations support a common role for RUK in both phragmoplast‐based cytokinesis in somatic cells and syncytial cytokinesis in reproductive cells.
Terahertz emission and detection both based on high-Tc superconductors: Towards an integrated receiver
2013-03-04

We have combined a stand-alone Bi2Sr2CaCu2O8 intrinsic Josephson junction stack, emitting terahertz radiation, with a YBa2Cu3O7 grain boundary Josephson junction acting as detector. The detector is mounted on a lens, positioned 1.2 cm away from the emitter on a similar lens. With the emitter radiating at 0.5 THz, we observed up to 7 Shapiro steps on the current-voltage characteristic of the detector. The ac current induced in this junction was 0.9 mA, and the dissipated power was 1.8 μW. The setup, although far from being optimized, may be considered as a first step towards an integrated high-Tc receiver.
Biodiversity Effects on Plant Stoichiometry
2013-03-04

In the course of the biodiversity-ecosystem functioning debate, the issue of multifunctionality of species communities has recently become a major focus. Elemental stoichiometry is related to a variety of processes reflecting multiple plant responses to the biotic and abiotic environment. It can thus be expected that the diversity of a plant assemblage alters community level plant tissue chemistry. We explored elemental stoichiometry in aboveground plant tissue (ratios of carbon, nitrogen, phosphorus, and potassium) and its relationship to plant diversity in a 5-year study in a large grassland biodiversity experiment (Jena Experiment). Species richness and functional group richness affected community stoichiometry, especially by increasing C:P and N:P ratios. The primacy of either species or functional group richness effects depended on the sequence of testing these terms, indicating that both aspects of richness were congruent and complementary to expected strong effects of legume presence and grass presence on plant chemical composition. Legumes and grasses had antagonistic effects on C:N (-27.7% in the presence of legumes, +32.7% in the presence of grasses). In addition to diversity effects on mean ratios, higher species richness consistently decreased the variance of chemical composition for all elemental ratios. The diversity effects on plant stoichiometry has several non-exclusive explanations: The reduction in variance can reflect a statistical averaging effect of species with different chemical composition or a optimization of nutrient uptake at high diversity, leading to converging ratios at high diversity. The shifts in mean ratios potentially reflect higher allocation to stem tissue as plants grew taller at higher richness. By showing a first link between plant diversity and stoichiometry in a multiyear experiment, our results indicate that losing plant species from grassland ecosystems will lead to less reliable chemical composition of forage for herbivorous consumers and belowground litter input.
Staphylococcus aureus Phenol-Soluble Modulin Peptides Modulate Dendritic Cell Functions and Increase In Vitro Priming of Regulatory T Cells
2013-03-05

Abstract The major human pathogen Staphylococcus aureus has very efficient strategies to subvert the human immune system. Virulence of the emerging community-associated methicillin-resistant S. aureus depends on phenol-soluble modulin (PSM) peptide toxins, which are known to attract and lyse neutrophils. However, their influences on other immune cells remain elusive. In this study, we analyzed the impact of PSMs on dendritic cells (DCs) playing an essential role in linking innate and adaptive immunity. In human neutrophils, PSMs exert their function by binding to the formyl peptide receptor (FPR) 2. We show that mouse DCs express the FPR2 homolog mFPR2 as well as its paralog mFPR1 and that PSMs are chemoattractants for DCs at noncytotoxic concentrations. PSMs reduced clathrin-mediated endocytosis and inhibited TLR2 ligand-induced secretion of the proinflammatory cytokines TNF, IL-12, and IL-6, while inducing IL-10 secretion by DCs. As a consequence, treatment with PSMs impaired the capacity of DCs to induce activation and proliferation of CD4+ T cells, characterized by reduced Th1 but increased frequency of FOXP3+ regulatory T cells. These regulatory T cells secreted high amounts of IL-10, and their suppression capacity was dependent on IL-10 and TGF-β. Interestingly, the induction of tolerogenic DCs by PSMs appeared to be independent of mFPRs, as shown by experiments with mice lacking mFPR2 (mFPR2−/−) and the cognate G protein (p110γ−/−). Thus, PSMs from highly virulent pathogens affect DC functions, thereby modulating the adaptive immune response and probably increasing the tolerance toward the pathogen.
Tom70 Is Essential for PINK1 Import into Mitochondria
2013-03-05

PTEN induced kinase 1 (PINK1) is a serine/threonine kinase in the outer membrane of mitochondria (OMM), and known as a responsible gene of Parkinson's disease (PD). The precursor of PINK1 is synthesized in the cytosol and then imported into the mitochondria via the translocase of the OMM (TOM) complex. However, a large part of PINK1 import mechanism remains unclear. In this study, we examined using cell-free system the mechanism by which PINK1 is targeted to and assembled into mitochondria. Surprisingly, the main component of the import channel, Tom40 was not necessary for PINK1 import. Furthermore, we revealed that the import receptor Tom70 is essential for PINK1 import. In addition, we observed that although PINK1 has predicted mitochondrial targeting signal, it was not processed by the mitochondrial processing peptidase. Thus, our results suggest that PINK1 is imported into mitochondria by a unique pathway that is independent of the TOM core complex but crucially depends on the import receptor Tom70.
Exhumation of the southern Pyrenean fold‐thrust belt (Spain) from orogenic growth to decay
2013-03-05

The deformation and exhumation history of an orogen reflects the interactions between tectonic and surface processes. We investigate orogenic wedge deformation, erosion, and sedimentation in the Pyrenees by (a) quantifying the spatiotemporal patterns of exhumation across the southern fold‐thrust belt (FTB) with bedrock apatite fission track (AFT) thermochronology and (b) comparing the results with existing deformation, exhumation, and sedimentation chronologies. Eighteen new samples record exhumation during and after orogenesis between 90 and 10 Ma. Rocks from the range core (Axial Zone) record rapid exhumation that progresses east to west and north to south, consistent with patterns of tectonically driven uplift. Synorogenic sediments shed into piggyback basins on the southern fold‐thrust belt during mountain building retain a detrital exhumation signal from the Axial Zone. In contrast, samples from other structural positions record exhumation of the thin‐skinned Pyrenean thrust sheets, suggesting sediment burial and heating of sufficient magnitudes to reset the AFT system (&gt;~3 km). In some locations, exhumation of these fold‐thrust structures is likely an erosional response to thrust‐driven rock uplift. We identify an exhumation phase ~25–20 Ma that occurs along the central and eastern Spanish Pyrenees at the boundary between thick‐ and thin‐skinned portions of the wedge. We suggest that this distributed exhumation event records (a) a taper response in the southern orogenic wedge to sediment loading and/or (b) a shift to wetter, stormier climate conditions following convergence‐driven uplift and full topographic development. A final exhumation phase between ~20 and 10 Ma may record the excavation of the southern fold‐thrust system following base level lowering in the Ebro Basin.
Potential of Akt mediated DNA repair in radioresistance of solid tumors overexpressing erbB-PI3K-Akt pathway
2013-03-05

Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key cascade downstream of several membrane-bound receptors, especially receptor tyrosine kinases such as erbB family members. This pathway is the most frequently activated pathway in human solid tumors. Akt/PKB (Protein Kinase B) members are the major kinases downstream of PI3K which are involved in a variety of cellular functions including growth, proliferation, survival, invasion, metastasis, and angiogenesis. Accumulated evidence indicates that activated Akt is a major predictive marker for the radiation response. Radiation-induced DNA double-strand break (DNA-DSB) is the prime cause of cell death induced by ionizing radiation. Preclinical in vitro and in vivo studies have shown that activated Akt1 accelerates repair of IR-induced DNA double-strand breaks (DNA-DSB) and, consequently, improves post-irradiation cell survival. Analyzing disregulations of Akt such as point mutations, gene amplification or overexpression, which result in constitutive activation of Akt might be of special importance in the context of radiotherapy outcome. Such studies as well as the mechanism(s) by which activated Akt1 regulates repair of DNA-DSB might help to combine the appropriate molecular targeting strategies with conventional radiotherapy to overcome radioresistance in solid tumors. Thus, in this review we discuss the disregulations in the components of upstream regulators of Akt as well as those specific modifications of AKT isoforms which enhance Akt activity. Likewise, mechanisms by which Akt improves post-irradiation cell survival will be reviewed. In this context, the role of Akt1 in repair of radiation-induced DNA-DSB will be discussed in more detail.
Studies Towards the Synthesis of Crotogoudin
2013-03-05

An effective synthesis of the tricyclic core structure of the new diterpene crotogoudin was achieved. The synthesis features an intermolecular domino Michael reaction to construct a bicyclo[2.2.2]octane motif and an aldol condensation to close ring B. Stork reductive alkylation with allyl bromide proceeded from the β side, resulting in the wrong stereochemistry at C-10.
Modelling Post‐Tree‐Harvesting Soil Erosion and Sediment Deposition Potential in the Turano River Basin (Italian Central Apennine)
2013-03-06

Abstract The overall aim of the paper is the assessment of human‐induced accelerated soil erosion processes due to forest harvesting in the Upper Turano River Basin. The spatio‐temporal pattern of soil erosion processes was investigated by means of a spatially distributed modelling approach. We used the Unit Stream Power Erosion and Deposition model. During the soil erosion‐modelling phase, the forest cover changes were mapped via remote sensing. According to this operation, the forest sectors exploited for timber production amounted to about 2781 ha or 9·9% of the wooded surface from March 2001 to August 2011. In this period, the average annual net soil erosion rate estimated by means of modelling operations totalled 0·83 Mg ha −1 y −1 for all the forest lands. The net soil erosion rate predicted for the disturbed forest lands is significantly higher than the average value for the entire forest (5·34 Mg ha −1 y −1 ). Estimates indicate a soil loss equal to 8521 Mg y −1 (net soil erosion 0·34 Mg ha −1 y −1 ) in the undisturbed forest area (254 km 2 ), whereas the 27·8 km 2 of disturbed forest area could potentially lose 14 846 Mg y −1 . The paper shows that a disturbed forest sector could produce about 74·2% more net erosion than a nine times larger, undisturbed forest sector. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Discovery of TeVγ-ray emission from PKS 0447-439 and derivation of an upper limit on its redshift
2013-03-06

Very high-energy γ-ray emission from PKS 0447−439 was detected with the H.E.S.S. Cherenkov telescope array in December 2009. This blazar is one of the brightest extragalactic objects in the Fermi bright source list and has a hard spectrum in the MeV to GeV range. In the TeV range, a photon index of 3.89 ± 0.37 (stat) ±0.22 (sys) and a flux normalisation at 1 TeV, Φ1 TeV = (3.5 ± 1.1(stat) ± 0.9(sys)) × 10-13 cm-2 s-1 TeV-1 were found. The detection with H.E.S.S. triggered observations in the X-ray band with the Swift and RXTE telescopes. Simultaneous UV and optical data from Swift UVOT and data from the optical telescopes ATOM and ROTSE are also available. The spectrum and light curve measured with H.E.S.S. are presented and compared to the multi-wavelength data at lower energies. A rapid flare is seen in the Swift XRT and RXTE data, together with a flux variation in the UV band, at a time scale of the order of one day. A firm upper limit of z &lt; 0.59 on the redshift of PKS 0447−439 is derived from the combined Fermi-LAT and H.E.S.S. data, given the assumptions that there is no upturn in the intrinsic spectrum above the Fermi-LAT energy range and that absorption on the extragalactic background light (EBL) is not weaker than the lower limit provided by current models. The spectral energy distribution is well described by a simple one-zone synchrotron self-Compton scenario, if the redshift of the source is less than z ≲ 0.4.
Drug Discovery: A Modern Decathlon
2013-03-06

The increasing costs as well as the lack of innovation potency in the development of new drugs have led to a discussion of the possible contribution of the German university landscape, especially pharmaceutical sciences. Successful examples are already apparent in the US.
Addendum to: Quasiparticle random phase approximation uncertainties and their correlations in the analysis of0νββdecay
2013-03-06

In a previous article [Phys. Rev. D 79, 053001 (2009)] we estimated the correlated uncertainties associated to the nuclear matrix elements (NME) of neutrinoless double beta decay (0 nu beta beta) within the quasiparticle random phase approximation (QRPA). Such estimates encompass recent independent calculations of NMEs, and can thus still provide a fair representation of the nuclear model uncertainties. In this context, we compare the claim of 0 nu beta beta decay in Ge-76 with recent negative results in Xe-136 and in other nuclei, and we infer the lifetime ranges allowed or excluded at 90% C.L. We also highlight some issues that should be addressed in order to properly compare and combine results coming from different 0 nu beta beta decay candidate nuclei.
Macular hole formation after toxoplasmic retinochoroiditis
2013-03-06

A 56-year-old female patient presented with toxoplasmic retinochoroiditis (TR) in the right eye. Optical coherence tomography revealed a full-thickness macular hole (MH) in the affected eye. Fluorescence angiography and indocyanine green-angiography disclosed focal choroidal ischaemia in the area of inflammation. Heidelberg retinal flowmetry confirmed the significant hypoperfusion in this area. Proper medication was administered. Ophthalmological examination 4 weeks later revealed an improvement of the clinical findings without visual restoration. This case supports the clinical hypothesis that retinochoroidal ischaemia due to TR may induce the development of MH, indicating that patients with TR may have a certain risk for MH formation.
True and false concerns about neuroenhancement: a response to ‘Neuroenhancers, addiction and research ethics’, by D M Shaw
2013-03-06

In his critical comment on our paper in this journal, Shaw argues that 'false assumptions' which we have criticised are in fact correct ('Neuroenhancers, addiction and research ethics'). He suggests that the risk of addiction to neuroenhancers may not be relevant, and that safety and research in regard to neuroenhancement do not pose unique ethical problems. Here, we demonstrate that Shaw ignores key empirical research results, trivialises addiction, commits logical errors, confuses addictions and passions, argues on a speculative basis, and fails to distinguish the specific ethical conditions of clinical research from those relevant for research in healthy volunteers. Therefore, Shaw's criticism cannot convince.
Alterations in Peripheral Blood B Cell Subsets and Dynamics of B Cell Responses during Human Schistosomiasis
2013-03-07

Antibody responses are thought to play an important role in control of Schistosoma infections, yet little is known about the phenotype and function of B cells in human schistosomiasis. We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in Gabonese schoolchildren with Schistosoma haematobium infection. Frequencies of memory B cell (MBC) subsets were increased, whereas naive B cell frequencies were reduced in the schistosome-infected group. At the functional level, isolated B cells from schistosome-infected children showed higher expression of the activation marker CD23 upon stimulation, but lower proliferation and TNF-α production. Importantly, 6-months after 3 rounds of praziquantel treatment, frequencies of naive B cells were increased, MBC frequencies were decreased and with the exception of TNF-α production, B cell responsiveness was restored to what was seen in uninfected children. These data show that S. haematobium infection leads to significant changes in the B cell compartment, both at the phenotypic and functional level.
Deoxyhypusine Hydroxylase from Plasmodium vivax, the Neglected Human Malaria Parasite: Molecular Cloning, Expression and Specific Inhibition by the 5-LOX Inhibitor Zileuton
2013-03-07

Primaquine, an 8-aminoquinoline, is the only drug which cures the dormant hypnozoites of persistent liver stages from P. vivax. Increasing resistance needs the discovery of alternative pathways as drug targets to develop novel drug entities. Deoxyhypusine hydroxylase (DOHH) completes hypusine biosynthesis in eukaryotic initiation factor (eIF-5A) which is the only cellular protein known to contain the unusual amino acid hypusine. Modified EIF-5A is important for proliferation of the malaria parasite. Here, we present the first successful cloning and expression of DOHH from P. vivax causing tertiary malaria. The nucleic acid sequence of 1041 bp encodes an open reading frame of 346 amino acids. Histidine tagged expression of P. vivax DOHH detected a protein of 39.01 kDa in E. coli. The DOHH protein from P. vivax shares significant amino acid identity to the simian orthologues from P. knowlesi and P. yoelii strain H. In contrast to P. falciparum only four E-Z-type HEAT-like repeats are present in P. vivax DOHH with different homology to phycocyanin lyase subunits from cyanobacteria and in proteins participating in energy metabolism of Archaea and Halobacteria. However, phycocyanin lyase activity is absent in P. vivax DOHH. The dohh gene is present as a single copy gene and transcribed throughout the whole erythrocytic cycle. Specific inhibition of recombinant P. vivax DOHH is possible by complexing the ferrous iron with zileuton, an inhibitor of mammalian 5-lipoxygenase (5-LOX). Ferrous iron in the active site of 5-LOX is coordinated by three conserved histidines and the carboxylate of isoleucine(673). Zileuton inhibited the P. vivax DOHH protein with an IC50 of 12,5 nmol determined by a relative quantification by GC/MS. By contrast, the human orthologue is only less affected with an IC50 of 90 nmol suggesting a selective iron-complexing strategy for the parasitic enzyme.