Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis.

Recent studies have established cell type- specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-kappaB. In each of these studies, inhibitors of NF-kappaB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To address whether Sindbis virus- induced NF-kappaB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-kappaB activity, regulates expression of gene products required for Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF-kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-kappaB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-kappaB activity relative to the death stimulus

Improvement of the Determination of the WIMP Mass from Direct Dark Matter Detection Data

Weakly Interacting Massive Particles (WIMPs) are one of the leading candidates for Dark Matter. We developed a model-independent method for determining the WIMP mass by using data (i.e., measured recoil energies) of direct detection experiments. Our method is independent of the as yet unknown WIMP density near the Earth, of the form of the WIMP velocity distribution, as well as of the WIMP-nucleus cross section. It requires however positive signals from at least two detectors with different target nuclei. At the first phase of this work we found a systematic deviation of the reconstructed WIMP mass from the real one for heavy WIMPs. Now we improved this method so that this deviation can be strongly reduced for even very high WIMP mass. The statistical error of the reconstructed mass has also been reduced. In a background-free evironment, a WIMP mass of ~ 50 GeV could in principle be determined with an error of ~ 35% with only 2 times 50 events.Comment: 3 pages, 2 figures, to appear in the SUSY08 proceeding

Higgs compositeness in Sp(2N)\mathrm{Sp}(2N) gauge theories --- Resymplecticisation, scale setting and topology

As part of an ongoing programme to study $\mathrm{Sp}(2N)$ gauge theories as potential realisations of composite Higgs models, we consider the case of $\mathrm{Sp}(4)$ on the lattice, both as a pure gauge theory, and with two Dirac fermion flavors in the fundamental representation. In order to compare results between these two cases and maintain control of lattice artefacts, we make use of the gradient flow to set the scale of the simulations. We present some technical aspects of the simulations, including preliminary results for the scale setting in the two cases and results for the topological charge history.Comment: 8 pages, 6 figures; talk presented at the 35th International Symposium on Lattice Field Theory, 18-24 June 2017, Granada, Spai

The attitude of dysphonic individuals towards others with dysphonia and their self-perception

This study examined three levels of self-concept in adults with voice disorders. The three levels are their self-perceived severity of voice problems, their meta-perception and their attitudes towards others with voice disorders. Eleven pairs of vocally healthy (vocally healthy listener group) and voice-disordered listeners (dysphonic listener group) were asked to give ratings on their self-perceived severity of their voice conditions, meta-perception and their attitudes towards individuals with different severities of voice disorders using semantic differential scale. The result showed that the dysphonic listener group gave significantly more negative ratings in their self-perceived severity and meta-perception than normal listener group. Similar attitude scores towards individuals with voice disorders were obtained from both listeners groups. The results suggested that voice-disordered individuals with voice disorders and speech therapists should not under-estimate the consequence of voice disorders. The study concluded that voice-disordered people individuals hold a generally negative attitude towards themselves. Limitations of the study and recommendations for future researches were discussed.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Thiol-norbornene photo-click hydrogels for tissue engineering applications.

Thiol-norbornene (thiol-ene) photo-click hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are cross-linked through light mediated orthogonal reactions between multi-functional norbornene-modified macromers (e.g., poly(ethylene glycol), hyaluronic acid, gelatin) and sulfhydryl-containing linkers (e.g., dithiothreitol, PEG-dithiol, bis-cysteine peptides) using low concentration of photoinitiator. The gelation of thiol-norbornene hydrogels can be initiated by long-wave UV light or visible light without additional co-initiator or co-monomer. The cross-linking and degradation behaviors of thiol-norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned owing to the orthogonal reactivity between norbornene and thiol moieties. Uniquely, the cross-linking of step-growth thiol-norbornene hydrogels is not oxygen-inhibited, therefore the gelation is much faster and highly cytocompatible compared with chain-growth polymerized hydrogels using similar gelation conditions. These hydrogels have been prepared as tunable substrates for 2D cell culture, as microgels or bulk gels for affinity-based or protease-sensitive drug delivery, and as scaffolds for 3D cell culture. Reports from different laboratories have demonstrated the broad utility of thiol-norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas-related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, as well as cancer cell biology. This article provides an up-to-date overview on thiol-norbornene hydrogel cross-linking and degradation mechanisms, tunable material properties, as well as the use of thiol-norbornene hydrogels in drug delivery and tissue engineering applications

Thiol-ene hydrogels as desmoplasia-mimetic matrices for modeling pancreatic cancer cell growth, invasion, and drug resistance

The development of pancreatic ductal adenocarcinoma (PDAC) is heavily influenced by local stromal tissues, or desmoplasia. Biomimetic hydrogels capable of mimicking tumor niches are particularly useful for discovering the role of independent matrix cues on cancer cell development. Here, we report a photo-curable and bio-orthogonal thiol-ene (i.e., cross-linked by mutually reactive norbornene and thiol groups via photoinitiation) hydrogel platform for studying the growth, morphogenesis, drug resistance, and cancer stem cell marker expression in PDAC cells cultured in 3D. The hydrogels were prepared from multi-arm poly(ethylene glycol)-norbornene cross-linked with protease-sensitive peptide to permit cell-mediated matrix remodeling. Collagen 1 fibrils were incorporated into the covalent network while cytokines (e.g., EGF and TGF-β1) were supplemented in the culture media for controlling cell fate. We found that the presence of collagen 1 enhanced cell proliferation and Yes-associated protein (YAP) translocation to cell nuclei. Cytokines and collagen 1 synergistically up-regulated MT1-MMP expression and induced cell spreading, suggestive of epithelial-mesenchymal transition (EMT) in the encapsulated cells. Furthermore, PDAC cells cultured in 3D developed chemo-resistance even in the absence of collagen 1 and cytokines. This phenotype is likely a consequence of the enrichment of pancreatic cancer stem cells that expressed high levels of CD24, sonic hedgehog (SHH), and vascular endothelial growth factor (VEGF)

Janus and Multifaced Supersymmetric Theories

We investigate the various properties Janus supersymmetric Yang-Mills theories. A novel vacuum structure is found and BPS monopoles and dyons are studied. Less supersymmetric Janus theories found before are derived by a simpler method. In addition, we find the supersymmetric theories when the coupling constant depends on two and three spatial coordinates.Comment: 20 pages, no figures, typos, equations corrected. Additional comment

Higgs compositeness in Sp(2N) gauge theories — Resymplecticisation, scale setting and topology

As part of an ongoing programme to study Sp(2N) gauge theories as potentialrealisations of composite Higgs models, we consider the case of Sp(4) on the lattice, bothas a pure gauge theory, and with two Dirac fermion flavors in the fundamental representation.In order to compare results between these two cases and maintain control oflattice artefacts, we make use of the gradient flow to set the scale of the simulations. Wepresent some technical aspects of the simulations, including preliminary results for thescale setting in the two cases and results for the topological charge history