A Hexa-Herbal TCM Decoction Used to Treat Skin Inflammation: An LC-MS-Based Phytochemical Analysis

In order to understand the chemical relationship between a traditional hexa-herbal Chinese medicine formula and botanical drugs it is derived from, an analytical platform comprising liquid chromatography coupled with triple quadrupole mass spectrometry and data mining was developed to separate and identify key chemical components. The hexa-herbal formula comprises the rootstock of Scutellaria baicalensis, Rheum tanguticum, Sophora flavescens, the root bark of Dictamnus dasycarpus, the bark of Phellodendron chinense, and the fruit of Kochia scoparia. Seventy-three compounds including alkaloids, anthraquinone derivatives, coumarins, coumarins derivatives, flavonoids, flavone glycosides, naphthalene derivatives, phenylbutanone glucopyranoside, phenolic acids, pterocarpans, stilbenes, stilbenes derivatives, and tannins were putatively identified based on mass measurement and characteristic fragment ions. Among the botanical drugs of the hexa-herbal Chinese medicine formula, the rootstock of R. tanguticum and S. flavescens, bark of P. chinense, and rootstock of S. baicalensis contributed to the majority of the extracted metabolites of the formula decoction. The developed method appeared to be a versatile tool for monitoring chemical constituents in extracts of a traditional Chinese medicine formula in a relatively comprehensive and systematic manner, and helped to understand the importance of the individual botanical drugs within a formulation

Aligning Manifolds of Double Pendulum Dynamics Under the Influence of Noise

This study presents the results of a series of simulation experiments that evaluate and compare four different manifold alignment methods under the influence of noise. The data was created by simulating the dynamics of two slightly different double pendulums in three-dimensional space. The method of semi-supervised feature-level manifold alignment using global distance resulted in the most convincing visualisations. However, the semi-supervised feature-level local alignment methods resulted in smaller alignment errors. These local alignment methods were also more robust to noise and faster than the other methods.Comment: The final version will appear in ICONIP 2018. A DOI identifier to the final version will be added to the preprint, as soon as it is availabl

The Regge Limit for Green Functions in Conformal Field Theory

We define a Regge limit for off-shell Green functions in quantum field theory, and study it in the particular case of conformal field theories (CFT). Our limit differs from that defined in arXiv:0801.3002, the latter being only a particular corner of the Regge regime. By studying the limit for free CFTs, we are able to reproduce the Low-Nussinov, BFKL approach to the pomeron at weak coupling. The dominance of Feynman graphs where only two high momentum lines are exchanged in the t-channel, follows simply from the free field analysis. We can then define the BFKL kernel in terms of the two point function of a simple light-like bilocal operator. We also include a brief discussion of the gravity dual predictions for the Regge limit at strong coupling.Comment: 23 pages 2 figures, v2: Clarification of relation of the Regge limit defined here and previous work in CFT. Clarification of causal orderings in the limit. References adde

Non-Redundant Spectral Dimensionality Reduction

Spectral dimensionality reduction algorithms are widely used in numerous domains, including for recognition, segmentation, tracking and visualization. However, despite their popularity, these algorithms suffer from a major limitation known as the "repeated Eigen-directions" phenomenon. That is, many of the embedding coordinates they produce typically capture the same direction along the data manifold. This leads to redundant and inefficient representations that do not reveal the true intrinsic dimensionality of the data. In this paper, we propose a general method for avoiding redundancy in spectral algorithms. Our approach relies on replacing the orthogonality constraints underlying those methods by unpredictability constraints. Specifically, we require that each embedding coordinate be unpredictable (in the statistical sense) from all previous ones. We prove that these constraints necessarily prevent redundancy, and provide a simple technique to incorporate them into existing methods. As we illustrate on challenging high-dimensional scenarios, our approach produces significantly more informative and compact representations, which improve visualization and classification tasks

Dendritic Spine Shape Analysis: A Clustering Perspective

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes

There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage

Persistence of magnetic field driven by relativistic electrons in a plasma

The onset and evolution of magnetic fields in laboratory and astrophysical plasmas is determined by several mechanisms, including instabilities, dynamo effects and ultra-high energy particle flows through gas, plasma and interstellar-media. These processes are relevant over a wide range of conditions, from cosmic ray acceleration and gamma ray bursts to nuclear fusion in stars. The disparate temporal and spatial scales where each operates can be reconciled by scaling parameters that enable to recreate astrophysical conditions in the laboratory. Here we unveil a new mechanism by which the flow of ultra-energetic particles can strongly magnetize the boundary between the plasma and the non-ionized gas to magnetic fields up to 10-100 Tesla (micro Tesla in astrophysical conditions). The physics is observed from the first time-resolved large scale magnetic field measurements obtained in a laser wakefield accelerator. Particle-in-cell simulations capturing the global plasma and field dynamics over the full plasma length confirm the experimental measurements. These results open new paths for the exploration and modelling of ultra high energy particle driven magnetic field generation in the laboratory

Classical Conformal Blocks and Accessory Parameters from Isomonodromic Deformations

Classical conformal blocks naturally appear in the large central charge limit of 2D Virasoro conformal blocks. In the $AdS_{3}/CFT_{2}$ correspondence, they are related to classical bulk actions and are used to calculate entanglement entropy and geodesic lengths. In this work, we discuss the identification of classical conformal blocks and the Painlev\'e VI action showing how isomonodromic deformations naturally appear in this context. We recover the accessory parameter expansion of Heun's equation from the isomonodromic $\tau$-function. We also discuss how the $c = 1$ expansion of the $\tau$-function leads to a novel approach to calculate the 4-point classical conformal block.Comment: 32+10 pages, 2 figures; v3: upgraded notation, discussion on moduli space and monodromies, numerical and analytic checks; v2: added refs, fixed emai

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation