Nonperturbative Effects from the Resummation of Perturbation Theory

Using the general argument in Borel resummation of perturbation theory that links the divergent perturbation theory to the nonperturbative effect we argue that the nonperturbative effect associated with the perturbation theory should have a branch cut only along the positive real axis in the complex coupling plane. The component in the weak coupling expansion of the nonperturbative amplitude, which usually includes the leading term in the weak coupling expansion, that gives rise to the branch cut can be calculated in principle from the perturbation theory combined with some exactly calculable properties of the nonperturbative effect. The realization of this mechanism is demonstrated in the double well potential and the two-dimensional O(N) nonlinear sigma model. In these models the leading term in weak coupling of the nonperturbative effect can be obtained with good accuracy from the first terms of the perturbation theory. Applying this mechanism to the infrared renormalon induced nonperturbative effect in QCD, we suggest some of the QCD condensate effects can be calculated in principle from the perturbation theory.Comment: 21 Pages, 1 Figure; To appear in Phys Rev

Anti-glycoprotein VI mediated immune thrombocytopenia: An under-recognized and significant entity?

Idiopathic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by relapsing/remitting thrombocytopenia. Bleeding complications are infrequent with platelet counts above 30x10(9)/L, and this level is commonly used as a threshold for treatment. The question of another/co-existent diagnosis or an alternate mechanism of platelet destruction arises when bleeding is experienced with platelet counts above this threshold. We report a case of anti-GPVI mediated ITP that was diagnosed following investigations performed to address this key clinical question. A patient with ITP experienced exaggerated bruising symptoms despite a platelet count of 91x10(9)/L. Platelet functional testing showed an isolated platelet defect of collagen-induced aggregation. Next generation sequencing excluded a pathogenic variant of GP6, and anti-GPVI antibodies that curtailed GPVI function were confirmed by extended platelet phenotyping. We propose that anti-GPVI mediated ITP may be under-recognized, and that inclusion of GPVI in antibody detection assays may improve their diagnostic utility and in turn, facilitate a better understanding of ITP pathophysiology and aid individualized treatment approaches

Football: a counterpoint to the procession of pain on the Western Front, 1914-1918?

In this article, three artworks of the First World War containing images of recreational football are analysed. These three images, In the Wings of the Theatre of War, Artillery Men at Football and Gassed, span the war from its beginning to its conclusion and are discussed in relationship to the development of recreational football in the front-line area, the evolving policies of censorship and propaganda and in consideration of the national mood in Britain. The paper shows how football went from being a spontaneous and improvised pastime in the early stages of the war to a well organized entertainment by war’s end. The images demonstrate how the war was portrayed as a temporary affair by a confident nation in 1914 to a more resigned acceptance of a semi-permanent event to be endured by 1918; however, all three artworks show that the sporting spirit, and hence the fighting spirit, of the British soldier was intact

Selective Roles for Tumor Necrosis Factor α-converting Enzyme/ADAM17 in the Shedding of the Epidermal Growth Factor Receptor Ligand Family: THE JUXTAMEMBRANE STALK DETERMINES CLEAVAGE EFFICIENCY

Epidermal growth factor (EGF) family ligands are derived by proteolytic cleavage of the ectodomains of integral membrane precursors. Previously, we established that tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) is a physiologic transforming growth factor-alpha (TGF-alpha) sheddase, and we also demonstrated enhanced shedding of amphiregulin (AR) and heparin-binding (HB)-EGF upon restoration of TACE activity in TACE-deficient EC-2 fibroblasts. Here we extended these results by showing that purified soluble TACE cleaved single sites in the juxtamembrane stalks of mouse pro-HB-EGF and pro-AR ectodomains in vitro. For pro-HB-EGF, this site matched the C terminus of the purified human growth factor, and we speculate that the AR cleavage site is also physiologically relevant. In contrast, ADAM9 and -10, both implicated in HB-EGF shedding, failed to cleave the ectodomain or cleaved at a nonphysiologic site, respectively. Cotransfection of TACE in EC-2 cells enhanced phorbol myristate acetate-induced but not constitutive shedding of epiregulin and had no effect on betacellulin (BTC) processing. Additionally, soluble TACE did not cleave the juxtamembrane stalks of either pro-BTC or pro-epiregulin ectodomains in vitro. Substitution of the shorter pro-BTC juxtamembrane stalk or truncation of the pro-TGF-alpha stalk to match the pro-BTC length reduced TGF-alpha shedding from transfected cells to background levels, whereas substitution of the pro-BTC P2-P2' sequence reduced TGF-alpha shedding less dramatically. Conversely, substitution of the pro-TGF-alpha stalk or lengthening of the pro-BTC stalk, especially when combined with substitution of the pro-TGF-alpha P2-P2' sequence, markedly increased BTC shedding. These results indicate that efficient TACE cleavage is determined by a combination of stalk length and scissile bond sequence

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids

Synthetic vectors based on reducible polycations consisting of histidine and polylysine residues (HIS RPCs) were evaluated for their ability to deliver nucleic acids. Initial experiments showed that RPC-based vectors with at least 70% histidine content mediated efficient levels of gene transfer without requirement for the endosomolytic agent chloroquine. Significant gene transfer was observed in a range of cell types achieving up to a 5-fold increase in the percentage of transfected cells compared to 25 kDa PEI, a gold standard synthetic vector. In contrast to 25 kDa PEI, HIS RPCs also mediated efficient transfer of other nucleic acids, including mRNA encoding green fluorescent protein in PC-3 cells and siRNA directed against the neurotrophin receptor p75(NTR) in post-mitotic cultures of rat dorsal root ganglion cell neurons. Experiments to elevate intracellular glutathione and linear profiling of cell images captured by multiphoton fluorescent microscopy highlighted that parameters such as the molecular weight and rate of cleavage of HIS RPCs were important factors in determining transfection activity. Altogether, these results demonstrate that HIS RPCs represent a novel and versatile type of vector that can be used for efficient cytoplasmic delivery of a broad range of nucleic acids. This should enable different or a combination of therapeutic strategies to be evaluated using a single type of polycation-based vector

Bilocal expansion of the Borel amplitude and the hadronic tau decay width

The singular part of Borel transform of a QCD amplitude near the infrared renormalon can be expanded in terms of higher order Wilson coefficients of the operators associated with the renormalon. In this paper we observe that this expansion gives nontrivial constraints on the Borel amplitude that can be used to improve the accuracy of the ordinary perturbative expansion of the Borel amplitude. In particular, we consider the Borel transform of the Adler function and its expansion around the first infrared renormalon due to the gluon condensate. Using the next-to-leading order Wilson coefficient of the gluon condensate operator, we obtain an exact constraint on the Borel amplitude at the first IR renormalon. We then extrapolate, using judiciously chosen conformal transformations and Pade approximants, the ordinary perturbative expansion of the Borel amplitude in such a way that this constraint is satisfied. This procedure allows us to predict the $O(\alpha_s^4)$ coefficient of the Adler function, which gives a result consistent with the estimate by Kataev and Starshenko using a completely different method. We then apply this improved Borel amplitude to the tau decay width, and obtain the strong coupling constant $\alpha_s(M_Z) =0.1193 \pm 0.0007_{exp.} \pm 0.0010_{EW+CKM} \pm 0.0009_{meth.} \pm 0.0003_{evol.}$. We then compare this result with those of other resummation methods.Comment: 30 pages, 4 eps-figures, revtex; version as appears in PRD; no major changes; more careful rounding of some number

Fresh air in the 21st century?

Ozone is an air quality problem today for much of the world's population. Regions can exceed the ozone air quality standards (AQS) through a combination of local emissions, meteorology favoring pollution episodes, and the clean-air baseline levels of ozone upon which pollution builds. The IPCC 2001 assessment studied a range of global emission scenarios and found that all but one projects increases in global tropospheric ozone during the 21st century. By 2030, near-surface increases over much of the northern hemisphere are estimated to be about 5 ppb (+2 to +7 ppb over the range of scenarios). By 2100 the two more extreme scenarios project baseline ozone increases of >20 ppb, while the other four scenarios give changes of -4 to +10 ppb. Even modest increases in the background abundance of tropospheric ozone might defeat current AQS strategies. The larger increases, however, would gravely threaten both urban and rural air quality over most of the northern hemisphere

Bacterial rotary export ATPases are allosterically regulated by the nucleotide second messenger cyclic-di-GMP

The widespread second messenger molecule cyclic di-GMP (cdG) regulates the transition from motile and virulent lifestyles to sessile, biofilm-forming ones in a wide range of bacteria. Many pathogenic and commensal bacterial-host interactions are known to be controlled by cdG signaling. Although the biochemistry of cyclic dinucleotide metabolism is well understood, much remains to be discovered about the downstream signaling pathways that induce bacterial responses upon cdG binding. As part of our ongoing research into the role of cdG signaling in plant-associated Pseudomonas species, we carried out an affinity capture screen for cdG binding proteins in the model organism Pseudomonas fluorescens SBW25. The flagella export AAA+ ATPase FliI was identified as a result of this screen and subsequently shown to bind specifically to the cdG molecule, with a KD in the low micromolar range. The interaction between FliI and cdG appears to be very widespread. In addition to FliI homologs from diverse bacterial species, high affinity binding was also observed for the type III secretion system homolog HrcN and the type VI ATPase ClpB2. The addition of cdG was shown to inhibit FliI and HrcN ATPase activity in vitro. Finally, a combination of site-specific mutagenesis, mass spectrometry, and in silico analysis was used to predict that cdG binds to FliI in a pocket of highly conserved residues at the interface between two FliI subunits. Our results suggest a novel, fundamental role for cdG in controlling the function of multiple important bacterial export pathways, through direct allosteric control of export ATPase proteins