Differential equations for multi-loop integrals and two-dimensional kinematics

In this paper we consider multi-loop integrals appearing in MHV scattering amplitudes of planar N=4 SYM. Through particular differential operators which reduce the loop order by one, we present explicit equations for the two-loop eight-point finite diagrams which relate them to massive hexagons. After the reduction to two-dimensional kinematics, we solve them using symbol technology. The terms invisible to the symbols are found through boundary conditions coming from double soft limits. These equations are valid at all-loop order for double pentaladders and allow to solve iteratively loop integrals given lower-loop information. Comments are made about multi-leg and multi-loop integrals which can appear in this special kinematics. The main motivation of this investigation is to get a deeper understanding of these tools in this configuration, as well as for their application in general four-dimensional kinematics and to less supersymmetric theories.Comment: 25 pages, 7 figure

Simplifying instanton corrections to N=4 SYM correlators

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Mellin Amplitudes for Dual Conformal Integrals

Motivated by recent work on the utility of Mellin space for representing conformal correlators in $AdS$/CFT, we study its suitability for representing dual conformal integrals of the type which appear in perturbative scattering amplitudes in super-Yang-Mills theory. We discuss Feynman-like rules for writing Mellin amplitudes for a large class of integrals in any dimension, and find explicit representations for several familiar toy integrals. However we show that the power of Mellin space is that it provides simple representations even for fully massive integrals, which except for the single case of the 4-mass box have not yet been computed by any available technology. Mellin space is also useful for exhibiting differential relations between various multi-loop integrals, and we show that certain higher-loop integrals may be written as integral operators acting on the fully massive scalar $n$-gon in $n$ dimensions, whose Mellin amplitude is exactly 1. Our chief example is a very simple formula expressing the 6-mass double box as a single integral of the 6-mass scalar hexagon in 6 dimensions.Comment: 29+7 page

Deficiency of RAMP1 Attenuates Antigen-Induced Airway Hyperresponsiveness in Mice

Asthma is a chronic inflammatory disease affecting the lung, characterized by breathing difficulty during an attack following exposure to an environmental trigger. Calcitonin gene-related peptide (CGRP) is a neuropeptide that may have a pathological role in asthma. The CGRP receptor is comprised of two components, which include the G-protein coupled receptor, calcitonin receptor-like receptor (CLR), and receptor activity-modifying protein 1 (RAMP1). RAMPs, including RAMP1, mediate ligand specificity in addition to aiding in the localization of receptors to the cell surface. Since there has been some controversy regarding the effect of CGRP on asthma, we sought to determine the effect of CGRP signaling ablation in an animal model of asthma. Using gene-targeting techniques, we generated mice deficient for RAMP1 by excising exon 3. After determining that these mice are viable and overtly normal, we sensitized the animals to ovalbumin prior to assessing airway resistance and inflammation after methacholine challenge. We found that mice lacking RAMP1 had reduced airway resistance and inflammation compared to wildtype animals. Additionally, we found that a 50% reduction of CLR, the G-protein receptor component of the CGRP receptor, also ameliorated airway resistance and inflammation in this model of allergic asthma. Interestingly, the loss of CLR from the smooth muscle cells did not alter the airway resistance, indicating that CGRP does not act directly on the smooth muscle cells to drive airway hyperresponsiveness. Together, these data indicate that signaling through RAMP1 and CLR plays a role in mediating asthma pathology. Since RAMP1 and CLR interact to form a receptor for CGRP, our data indicate that aberrant CGRP signaling, perhaps on lung endothelial and inflammatory cells, contributes to asthma pathophysiology. Finally, since RAMP-receptor interfaces are pharmacologically tractable, it may be possible to develop compounds targeting the RAMP1/CLR interface to assist in the treatment of asthma

Holographic current correlators at finite coupling and scattering off a supersymmetric plasma

By studying the effect of the order(\alpha'^3) string theory corrections to type IIB supergravity, including those corrections involving the Ramond-Ramond five-form field strength, we obtain the corrected equations of motion of an Abelian perturbation of the AdS_5-Schwarzschild black hole. We then use the gauge theory/string theory duality to examine the coupling-constant dependence of vector current correlators associated to a gauged U(1) sub-group of the global R-symmetry group of strongly-coupled N=4 supersymmetric Yang-Mills theory at finite temperature. The corrections induce a set of higher-derivative operators for the U(1) gauge field, but their effect is highly suppressed. We thus find that the order(\alpha'^3) corrections affect the vector correlators only indirectly, through the corrected metric. We apply our results to investigate scattering off a supersymmetric Yang-Mills plasma at low and high energy. In the latter regime, where Deep Inelastic Scattering is expected to occur, we find an enhancement of the plasma structure functions in comparison with the infinite 't Hooft coupling result.Comment: 38 pages, 6 figures, minor clarifications added, typos corrected, references adde

Plasma photoemission from string theory

Leading 't Hooft coupling corrections to the photoemission rate of the planar limit of a strongly-coupled {\cal {N}}=4 SYM plasma are investigated using the gauge/string duality. We consider the full order \alpha'^3 type IIB string theory corrections to the supergravity action, including higher order terms with the Ramond-Ramond five-form field strength. We extend our previous results presented in arXiv:1110.0526. Photoemission rates depend on the 't Hooft coupling, and their curves suggest an interpolating behaviour from strong towards weak coupling regimes. Their slopes at zero light-like momentum give the electrical conductivity as a function of the 't Hooft coupling, in full agreement with our previous results of arXiv:1108.6306. Furthermore, we also study the effect of corrections beyond the large N limit.Comment: 36 pages, 5 figures, paragraph added in the conclusions, references added, typos correcte

Expansion and Harvesting of hMSC-TERT

The expansion of human mesenchymal stem cells as suspension culture by means of spinner flasks and microcarriers, compared to the cultivation in tissue culture flasks, offers the advantage of reducing the requirements of large incubator capacities as well as reducing the handling effort during cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of hMSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d-1. The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin-accutase mix was most effective. After spinner expansion and harvesting the cells were successfully differentiated to adipocytes

Adaptation of the protein translational apparatus during ATDC5 chondrogenic differentiation.

IntroductionRibosome biogenesis is integrated with many cellular processes including proliferation, differentiation and oncogenic events. Chondrogenic proliferation and differentiation require a high cellular translational capacity to facilitate cartilaginous extracellular matrix production. We here investigated the expression dynamics of factors involved in ribosome biogenesis during in vitro chondrogenic differentiation and determined whether protein translation capacity adapts to different phases of chondrogenic differentiation.MaterialsSnoRNA expression during ATDC5 differentiation was analyzed by RNA sequencing of samples acquired from day 0 (progenitor stage), 7 (chondrogenic stage) and day 14 (hypertrophic stage). RT-qPCR was used to determine expression of fibrillarin, dyskerin, UBF-1, Sox9, Col2a1, Runx2, Col10a1 mRNAs and 18S, 5.8S and 28S rRNAs. Protein expression of fibrillarin, dyskerin and UBF-1 was determined by immunoblotting. Ribosomal RNA content per cell was determined by calculating rRNA RT-qPCR signals relative to DNA content (SYBR Green assay). Total protein translational activity was evaluated with a puromycilation assay and polysome profiling.ResultsAs a result of initiation of chondrogenic differentiation (Δt0-t7), 21 snoRNAs were differentially expressed (DE). Hypertrophic differentiation caused DE of 23 snoRNAs (Δt7-t14) and 43 when t0 was compared to t14. DE snoRNAs, amongst others, target nucleotide modifications in the 28S rRNA peptidyl transferase center and the 18S rRNA decoding center. UBF-1, fibrillarin and dyskerin expression increased as function of differentiation and displayed highest fold induction at day 5-6 in differentiation. Ribosomal RNA content per cell was significantly increased at day 7, but not at day 14 in differentiation. Similar dynamics in translational capacity and monosomal ribosome fraction were observed during differentiation.ConclusionThe expression of a great number of ribosome biogenesis factors is altered during chondrogenic differentiation of ATDC5 cells, which is accompanied by significant changes in cellular translational activity. This elucidation of ribosome biogenesis dynamics in chondrogenic differentiation models enables the further understanding of the role of ribosome biogenesis and activity during chondrocyte cell commitment and their roles in human skeletal development diseases

The antiviral protein viperin regulates chondrogenic differentiation via CXCL10 protein secretion.

Viperin (also known as radical SAM domain-containing 2, RSAD2) is an interferon-inducible and evolutionary conserved protein that participates in the cell's innate immune response against a number of viruses. Viperin mRNA is a substrate for endoribonucleolytic cleavage by RNase mitochondrial RNA processing (MRP) and mutations in the RMRP small nucleolar RNA (snoRNA) subunit of the RNase MRP complex cause cartilage-hair hypoplasia (CHH), a human developmental condition characterized by metaphyseal chondrodysplasia and severe dwarfism. It is unknown how CHH-pathogenic mutations in RMRP snoRNA interfere with skeletal development and aberrant processing of RNase MRP substrate RNAs is thought to be involved. We hypothesized that viperin plays a role in chondrogenic differentiation. Using immunohistochemistry, RT-qPCR, immunoblotting, ELISA, siRNA-mediated gene silencing, plasmid-mediated gene overexpression, label-free mass-spectrometry proteomics and promoter reporter bioluminescence assays, we discovered here that viperin is expressed in differentiating chondrocytic cells and regulates their protein secretion and the outcome of chondrogenic differentiation by influencing transforming growth factor β (TGF-β)/SMAD family 2/3 (SMAD2/3) activity via C-X-C motif chemokine ligand 10 (CXCL10). Of note, we observed disturbances in this viperin-CXCL10-TGF-β/SMAD2/3 axis in CHH chondrocytic cells. Our results indicate that the anti-viral protein viperin controls chondrogenic differentiation by influencing secretion of soluble proteins and identify a molecular route that may explain impaired chondrogenic differentiation of cells from individuals with CHH

Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival

The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30–64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35–p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis. © 1999 Cancer Research Campaig