A Family of Joint Sparse PCA Algorithms for Anomaly Localization in Network Data Streams

Determining anomalies in data streams that are collected and transformed from various types of networks has recently attracted significant research interest. Principal Component Analysis (PCA) is arguably the most widely applied unsupervised anomaly detection technique for networked data streams due to its simplicity and efficiency. However, none of existing PCA based approaches addresses the problem of identifying the sources that contribute most to the observed anomaly, or anomaly localization. In this paper, we first proposed a novel joint sparse PCA method to perform anomaly detection and localization for network data streams. Our key observation is that we can detect anomalies and localize anomalous sources by identifying a low dimensional abnormal subspace that captures the abnormal behavior of data. To better capture the sources of anomalies, we incorporated the structure of the network stream data in our anomaly localization framework. Also, an extended version of PCA, multidimensional KLE, was introduced to stabilize the localization performance. We performed comprehensive experimental studies on four real-world data sets from different application domains and compared our proposed techniques with several state-of-the-arts. Our experimental studies demonstrate the utility of the proposed methods

Mechanisms of Resistance against B Cell Targeting Treatments for Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder caused by autoantibodies that disrupt neuromuscular transmission by targeting components of neuromuscular junctions, such as the acetylcholine receptor (AChR, 90% of patients) and muscle specific kinase (MuSK, 10% of patients). Treatments that address the underlying causes of MG target the cells responsible for producing these autoantibodies. Two such treatment strategies are predominantly used: (1) surgical resection of the thymus (a reservoir for auto-antigen specific B cells in patients with AChR MG) and (2) systemic therapy targeting subsets of autoantibody-producing B cells. The thymus is a known anatomic reservoir for B cells that can produce pathogenic AChR autoantibodies, and resection of the thymus has long been known to improve MG symptoms. However, many patients also fail to achieve complete remission after thymectomy. Rituximab (RTX) is a B cell depleting agent used in the management of an increasingly wide range of autoimmune diseases. Many AChR and MuSK MG patients achieve remission after RTX but relapse following treatment cessation can occur for some patients. In both cases, I was interested in testing the possibility that the failed depletion of B cells relevant to disease may drive poor responses

Exploring Be phenomena in OBA stars: a Mid-infrared search

As early-type stars with a rotation speed close to their critical velocity, Be stars experience an event called the Be phenomenon. The material in their equator is ejected into outside space during the Be phenomenon and forms a circumstellar disk. The mechanism triggering these events remains poorly understood, and observations of these events are limited because the duration of these events ranges from months to years. Long-term epoch photometry in the infrared bands is expected to be ideal for detecting Be phenomena because the brightness variation is larger, and the effect of interstellar extinction is weaker as well. We conducted a systematic search for Be phenomena among Milky Way OBA stars in the mid-infrared. We examined the brightness and colour variations of known classical Be stars using the WISE W1 and W2 photometry bands to quantify their characteristics. Subsequently, we established a set of criteria to identify similar photometric variations in a large sample of OBA stars. We found 916 OBA stars that show Be phenomena in the past 13 years, 736 of which are newly discovered. The peak-to-peak variations in magnitude and colour were found to be correlated, indicating that a decretion disk is common. The increase in colour was observed to be strongly correlated with the emission of the H-alpha line, providing further evidence of the association with circumstellar disks. The brightness variation of a star with Be phenomena can be up to 1.5 mag, and the colour variations can be up to 0.4 mag. The median durations for the disk build-up and decay phases are 474 and 524 days, respectively (durations shorter than 180 days are not sampled). The search for Be phenomena in the WISE bands greatly enlarges the number of stars showing disk variation, and it enables multi-band photometry analysis of these events with the help of current and future optical photometry surveys.Comment: 14 pages, 16 figures, 5 tables, accepted for publication in A&

Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology.

Myasthenia gravis (MG) is a prototypical autoantibody mediated disease. The autoantibodies in MG target structures within the neuromuscular junction (NMJ), thus affecting neuromuscular transmission. The major disease subtypes of autoimmune MG are defined by their antigenic target. The most common target of pathogenic autoantibodies in MG is the nicotinic acetylcholine receptor (AChR), followed by muscle-specific kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4). MG patients present with similar symptoms independent of the underlying subtype of disease, while the immunopathology is remarkably distinct. Here we highlight these distinct immune mechanisms that describe both the B cell- and autoantibody-mediated pathogenesis by comparing AChR and MuSK MG subtypes. In our discussion of the AChR subtype, we focus on the role of long-lived plasma cells in the production of pathogenic autoantibodies, the IgG1 subclass mediated pathology, and contributions of complement. The similarities underlying the immunopathology of AChR MG and neuromyelitis optica (NMO) are highlighted. In contrast, MuSK MG is caused by autoantibody production by short-lived plasmablasts. MuSK MG autoantibodies are mainly of the IgG4 subclass which can undergo Fab-arm exchange (FAE), a process unique to this subclass. In FAE IgG4, molecules can dissociate into two halves and recombine with other half IgG4 molecules resulting in bispecific antibodies. Similarities between MuSK MG and other IgG4-mediated autoimmune diseases, including pemphigus vulgaris (PV) and chronic inflammatory demyelinating polyneuropathy (CIDP), are highlighted. Finally, the immunological distinctions are emphasized through presentation of biological therapeutics that provide clinical benefit depending on the MG disease subtype

Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving

The poor efficacy of seasonal influenza virus vaccines is often attributed to pre-existing immunity interfering with the persistence and maturation of vaccine-induced B cell responses. We previously showed that a subset of vaccine-induced B cell lineages are recruited into germinal centers (GCs) following vaccination, suggesting that affinity maturation of these lineages against vaccine antigens can occur. However, it remains to be determined whether seasonal influenza vaccination stimulates additional evolution of vaccine-specific lineages, and previous work has found no significant increase in somatic hypermutation among influenza-binding lineages sampled from the blood following seasonal vaccination in humans. Here, we investigate this issue using a phylogenetic test of measurable immunoglobulin sequence evolution. We first validate this test through simulations and survey measurable evolution across multiple conditions. We find significant heterogeneity in measurable B cell evolution across conditions, with enrichment in primary response conditions such as HIV infection and early childhood development. We then show that measurable evolution following influenza vaccination is highly compartmentalized: while lineages in the blood are rarely measurably evolving following influenza vaccination, lineages containing GC B cells are frequently measurably evolving. Many of these lineages appear to derive from memory B cells. We conclude from these findings that seasonal influenza virus vaccination can stimulate additional evolution of responding B cell lineages, and imply that the poor efficacy of seasonal influenza vaccination is not due to a complete inhibition of vaccine-specific B cell evolution

The influence of the extraction method on bioactivity of the root of Tetrastigma hemsleyanum

Tetrastigma hemsleyanum is traditionally used as a folk medicine and functional food in China. Its extracts have been confirmed to have many bioactivities. However, the effect of extracting temperature on its bioactivity has not been reported. In this research, the total flavonoids content (TFC), total polyphenol content (TPC), antiproliferative, antioxidant, and anti‐inflammatory activities of ethanol extracts and water extracts (extracted at 55, 70, 85, and 100°C) were observed. The results indicated that ethanol extracts showed better antioxidant activity with DPPH EC50 of 504.1 ± 3.8 μg/ml and ABTS EC50 of 851.4 ± 3.9 μg/ml. A better antiproliferative activity on HepG2, PC12, Caco‐2, and Hela cells was observed on ethanol extracts. The results of anti‐inflammatory activities also indicated that all of the extracts can reduce the NO production of LPS‐stimulated macrophage with dose‐independent manner. In summary, the results showed that the antiproliferative, antioxidant, and anti‐inflammatory activities of water extracts decreased with the increasing temperature to some extent