Approximate Frank-Wolfe Algorithms over Graph-structured Support Sets

In this paper, we propose approximate Frank-Wolfe (FW) algorithms to solve convex optimization problems over graph-structured support sets where the \textit{linear minimization oracle} (LMO) cannot be efficiently obtained in general. We first demonstrate that two popular approximation assumptions (\textit{additive} and \textit{multiplicative gap errors)}, are not valid for our problem, in that no cheap gap-approximate LMO oracle exists in general. Instead, a new \textit{approximate dual maximization oracle} (DMO) is proposed, which approximates the inner product rather than the gap. When the objective is $L$-smooth, we prove that the standard FW method using a $\delta$-approximate DMO converges as $\mathcal{O}(L / \delta t + (1-\delta)(\delta^{-1} + \delta^{-2}))$ in general, and as $\mathcal{O}(L/(\delta^2(t+2)))$ over a $\delta$-relaxation of the constraint set. Additionally, when the objective is $\mu$-strongly convex and the solution is unique, a variant of FW converges to $\mathcal{O}(L^2\log(t)/(\mu \delta^6 t^2))$ with the same per-iteration complexity. Our empirical results suggest that even these improved bounds are pessimistic, with significant improvement in recovering real-world images with graph-structured sparsity.Comment: 30 pages, 8 figure

Fast Online Node Labeling for Very Large Graphs

This paper studies the online node classification problem under a transductive learning setting. Current methods either invert a graph kernel matrix with $\mathcal{O}(n^3)$ runtime and $\mathcal{O}(n^2)$ space complexity or sample a large volume of random spanning trees, thus are difficult to scale to large graphs. In this work, we propose an improvement based on the \textit{online relaxation} technique introduced by a series of works (Rakhlin et al.,2012; Rakhlin and Sridharan, 2015; 2017). We first prove an effective regret $\mathcal{O}(\sqrt{n^{1+\gamma}})$ when suitable parameterized graph kernels are chosen, then propose an approximate algorithm FastONL enjoying $\mathcal{O}(k\sqrt{n^{1+\gamma}})$ regret based on this relaxation. The key of FastONL is a \textit{generalized local push} method that effectively approximates inverse matrix columns and applies to a series of popular kernels. Furthermore, the per-prediction cost is $\mathcal{O}(\text{vol}({\mathcal{S}})\log 1/\epsilon)$ locally dependent on the graph with linear memory cost. Experiments show that our scalable method enjoys a better tradeoff between local and global consistency.Comment: 40 pages,17 figures, ICML 202

Extended direct lysis method for virus detection on berries including droplet digital RT-PCR or real time RT-PCR with reduced influence from inhibitors

Detection of viruses on berries is a challenging task, often hampered by the presence of RT-qPCR inhibiting substances from berry juice. A direct extraction method for virus detection (murine norovirus and GA phage) on frozen raspberries was previously published. We expanded (different types of berries and viruses) and improved the method using MobiSpin S400 columns that filter nucleic acids based on size-exclusion chromatography. While no inhibition was detected in filtered RNA, unfiltered RNA needed from 1:2 to more than 1:8 dilution in order to remove inhibition. The modified method gave recoveries of bovine norovirus around 40.8 ± 4.5% (40.0 ± 7.0%), 48.0 ± 26.0% (50.5 ± 7.8%), 28.3 ± 2.6% (45.8 ± 6.6%) from frozen (fresh) raspberries, strawberries and blueberries, respectively. For the same samples, recoveries of hepatitis A virus were 34.0 ± 5.9% (34.0 ± 6.0%), 40.0 ± 13.3% (34.2 ± 10.5%) and 23.0 ± 6.8% (31.5 ± 7.9%). For adenovirus40 (DNA virus), recoveries were 21.2 ± 8.6%, 16.0 ± 3.2% and 5.7 ± 0.2% from fresh raspberries, strawberries and blueberries respectively and column filtration did not add any improved effect. The modified method is effective and timesaving for detection of viral RNA from both fresh and frozen berries. As an emerging detection and direct quantification method, droplet digital RT-PCR was compared to RT-qPCR and was much less influenced by inhibitors when detecting mengovirus in unfiltered RNA from berries. However, for low levels of pure RNA, RT-qPCR showed slightly higher sensitivity and more stable results

Fibre optic chemical sensor based on graphene oxide-coated long period grating

In this work, a graphene oxide-coated long period fibre grating (GO-LPG) is proposed for chemical sensing application. Graphene oxide (GO) has been deposited on the surface of long period grating to form a sensing layer which significantly enhances the interaction between LPG propagating light and the surrounding-medium. The sensing mechanism of GO-LPG relies on the change of grating resonance intensity against surrounding-medium refractive index (SRI). The proposed GO-LPG has been used to measure the concentrations of sugar aqueous solutions. The refractive index sensitivities with 99.5 dB/RIU in low refractive index region (1.33-1.35) and 320.6 dB/RIU in high index region (1.42-1.44) have been achieved, showing an enhancement by a factor of 3.2 and 6.8 for low and high index regions, respectively. The proposed GO-LPG can be further extended to the development of optical biochemical sensor with advantages of high sensitivity, real-time and label-free sensing

Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts

Mammalian IRF9 and STAT2, together with STAT1, form the ISGF3 transcription factor complex, which is critical for type I interferon (IFN)-induced signaling, while IFNγ stimulation is mediated by homodimeric STAT1 protein. Teleost fish are known to possess most JAK and STAT family members, however, description of their functional activity in lower vertebrates is still scarce. In the present study we have identified two different STAT2 homologs and one IRF9 homolog from Atlantic salmon (Salmo salar). Both proteins have domain-like structures with functional motifs that are similar to higher vertebrates, suggesting that they are orthologs to mammalian STAT2 and IRF9. The two identified salmon STAT2s, named STAT2a and STAT2b, showed high sequence identity but were divergent in their transactivation domain (TAD). Like STAT1, ectopically expressed STAT2a and b were shown to be tyrosine phosphorylated by type I IFNs and, interestingly, also by IFNγ. Microscopy analyses demonstrated that STAT2 co-localized with STAT1a in the cytoplasm of unstimulated cells, while IFNa1 and IFNγ stimulation seemed to favor their nuclear localization. Overexpression of STAT2a or STAT2b together with STAT1a activated a GAS-containing reporter gene construct in IFNγ-stimulated cells. The highest induction of GAS promoter activation was found in IFNγ-stimulated cells transfected with IRF9 alone. Taken together, these data suggest that salmon STAT2 and IRF9 may have a role in IFNγ-induced signaling and promote the expression of GAS-driven genes in bony fish. Since mammalian STAT2 is primarily an ISGF3 component and not involved in IFNγ signaling, our finding features a novel role for STAT2 in fish

Biodegradable double-network GelMA-ACNM hydrogel microneedles for transdermal drug delivery

As a minimally invasive drug delivery platform, microneedles (MNs) overcome many drawbacks of the conventional transdermal drug delivery systems, therefore are favorable in biomedical applications. Microneedles with a combined burst and sustained release profile and maintained therapeutic molecular bioactivity could further broaden its applications as therapeutics. Here, we developed a double-network microneedles (DN MNs) based on gelatin methacrylate and acellular neural matrix (GelMA-ACNM). ACNM could function as an early drug release matrix, whereas the addition of GelMA facilitates sustained drug release. In particular, the double-network microneedles comprising GelMA-ACNM hydrogel has distinctive biological features in maintaining drug activity to meet the needs of application in treating different diseases. In this study, we prepared the double-network microneedles and evaluated its morphology, mechanical properties, drug release properties and biocompatibility, which shows great potential for delivery of therapeutic molecules that needs different release profiles in transdermal treatment

Gene structure and transcription of IRF-2 in the mandarin fish Siniperca chuatsi with the finding of alternative transcripts and microsatellite in the coding region

The gene of interferon regulatory factor-2 (IRF-2) has been cloned from the mandarin fish (Siniperca chuatsi). The IRF-2 gene has 6,418 nucleotides (nt) and contains eight exons and seven introns, encoding two mRNAs. The two IRF-2 mRNAs each contained an open reading frame of 873 nt, which both translate into the same 291 amino acids but differed in their 5' untranslated region: one mRNA was transcribed initially from the exon 1 bypassing exon 2, while the other was transcribed from the exon 2. The microsatellites (CA repeats) could be found in the carboxyl terminal region of mandarin fish IRF-2, which result in the truncated form molecules. The microsatellites' polymorphism was investigated, and eight alleles were found in 16 individuals. The microsatellites were also examined in IRF-2 of several freshwater perciform fishes. The transcription of the IRF-2 in different tissues with or without poly inosine-cytidine stimulation was analyzed by real-time PCR, and the constitutive transcription of both molecules could be detected in all the tissues examined.The gene of interferon regulatory factor-2 (IRF-2) has been cloned from the mandarin fish (Siniperca chuatsi). The IRF-2 gene has 6,418 nucleotides (nt) and contains eight exons and seven introns, encoding two mRNAs. The two IRF-2 mRNAs each contained an open reading frame of 873 nt, which both translate into the same 291 amino acids but differed in their 5' untranslated region: one mRNA was transcribed initially from the exon 1 bypassing exon 2, while the other was transcribed from the exon 2. The microsatellites (CA repeats) could be found in the carboxyl terminal region of mandarin fish IRF-2, which result in the truncated form molecules. The microsatellites' polymorphism was investigated, and eight alleles were found in 16 individuals. The microsatellites were also examined in IRF-2 of several freshwater perciform fishes. The transcription of the IRF-2 in different tissues with or without poly inosine-cytidine stimulation was analyzed by real-time PCR, and the constitutive transcription of both molecules could be detected in all the tissues examined

Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

Edaravone (EDA) is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA-) induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs) and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities

Extended direct lysis method for virus detection on berries including droplet digital RT-PCR or real time RT-PCR with reduced influence from inhibitors

Detection of viruses on berries is a challenging task, often hampered by the presence of RT-qPCR inhibiting substances from berry juice. A direct extraction method for virus detection (murine norovirus and GA phage) on frozen raspberries was previously published. We expanded (different types of berries and viruses) and improved the method using MobiSpin S400 columns that filter nucleic acids based on size-exclusion chromatography. While no inhibition was detected in filtered RNA, unfiltered RNA needed from 1:2 to more than 1:8 dilution in order to remove inhibition. The modified method gave recoveries of bovine norovirus around 40.8 ± 4.5% (40.0 ± 7.0%), 48.0 ± 26.0% (50.5 ± 7.8%), 28.3 ± 2.6% (45.8 ± 6.6%) from frozen (fresh) raspberries, strawberries and blueberries, respectively. For the same samples, recoveries of hepatitis A virus were 34.0 ± 5.9% (34.0 ± 6.0%), 40.0 ± 13.3% (34.2 ± 10.5%) and 23.0 ± 6.8% (31.5 ± 7.9%). For adenovirus40 (DNA virus), recoveries were 21.2 ± 8.6%, 16.0 ± 3.2% and 5.7 ± 0.2% from fresh raspberries, strawberries and blueberries respectively and column filtration did not add any improved effect. The modified method is effective and timesaving for detection of viral RNA from both fresh and frozen berries. As an emerging detection and direct quantification method, droplet digital RT-PCR was compared to RT-qPCR and was much less influenced by inhibitors when detecting mengovirus in unfiltered RNA from berries. However, for low levels of pure RNA, RT-qPCR showed slightly higher sensitivity and more stable results

Identification of apoptosis-related genes and transcription variations in response to microcystin-LR in zebrafish liver

There is growing evidence that the effects of microcystin-LR (MC-LR) are closely related to apoptosis. This study utilized microarray to identify the apoptosis-related genes induced by MC-LR in zebrafish liver. The messenger RNA abundance of some apoptosis-related genes was found to be increased, including five tumor necrosis factor (TNF)-related members (apoptosis regulatory protein siva, tumor necrosis factor-alpha (tnfa) TNF (ligand) superfamily member 10 (tnfsf10), TNF-inducible protein 6 (tnfaip6) and TNF receptor associated factor 2 binding protein (traf2bp)), three p53-related genes (tumor protein p53 inducible nuclear protein 1 (tp53inp1), p53-induced protein phosphatase 1 (ppm1d) and a novel apoptosis stimulating protein of p53 (aspp2)), bcl 2 family members (proapoptosis gene bax and antiapoptosis gene mcl 1), caspases (caspase y (caspy) and a PYD and CARD domain-containing protein (pycard)) and the transforming growth factor beta (TGF-beta) induced apoptosis protein 2 (taip2). Real-time polymerase chain reaction was used to study the kinetic transcriptional changes in seven apoptosis-related genes. Elevated transcription of p53, tp53inp1, mcl 1 and taip2 could only be detected at 6 h, increased transcription of the antagonist molecules, bcl 2 and bax could be detected at most time points and the significant change of caspy could be found at 48 h and 72 h after stimulation. Taken together, the results obtained in the present study clearly demonstrate that large amount of apoptosis-related genes are involved in the regulation of MC-LR-induced apoptosis