Molecular and Genomic Investigations of the Role of MAP3K8 in IL-1β-Induced Response in Respiratory Epithelial Cells

Mitogen Activated Protein 3 Kinase 8 (MAP3K8) is a member of the serine/threonine protein kinase family and has been demonstrated to be involved in the mitogen activated protein kinase (MAPK) pathway. The latter pathway plays an important role in many aspects of the immune mediated inflammatory response. Inhibition of MAP3K8 in primary human cell types decreases the production of TNF-α and other pro-inflammatory mediators during inflammatory events. Pharmacologic inhibition of MAP3K8 has been shown to be an appropriate therapeutic target for rheumatoid arthritis and other human inflammatory diseases. Inhibition of MAP3K8 may therefore potentially be a new therapeutic strategy for airway inflammation. Investigation of the role of MAP3K8 in regulation of the inflammatory response was conducted using epithelial cell lines. A MAP3K8 gene knockdown experiment using small interfering RNA (siRNA) was carried out to establish the effect of MAP3K8 on the inflammatory response following IL-1β stimulation. In addition the effect of MAP3K8 gene knockdown on the therapeutic outcome of dexamethasone (Dex) was investigated. ELISAs were used to establish whether knockdown of MAP3K8 resulted in inhibition of IL-1β-induced IL-6, IL-8 and RANTES. The effect of treatment with Dex in combination with MAP3K8 gene silencing on ERK and MEK phosphorylation was determined by Western Blotting. The impact of MAP3K8 gene silencing on global gene expression was also assessed using Affymetrix Human Gene 1.1ST arrays. Differential expression and network analyses were performed on the data generated. A significant rise in MAP3K8 gene expression was found 2 hours after IL-1β stimulation in both A549 and normal human bronchial epithelial (NHBE) cells. In addition, siRNA against MAP3K8 resulted in approximately 40% inhibition of IL-6, IL-8 and RANTES expression after IL-1β stimulation. Furthermore, MAP3K8 gene silencing enhanced by approximately 40% the decrease in IL-8 and RANTES release seen at different concentrations of Dex. The combination of MAP3K8 gene silencing and Dex also resulted in a greater inhibition of phosphorylated ERK compared to that seen with Dex alone. Data from global gene expression arrays revealed that the MAP3K8 regulated inflammatory response was predominantly involved in the ERK/MAPK and SAPK/JNK pathways but not the p38 MAPK pathway. Among the genes regulated by MAP3K8, it is interesting to note that IL-6, MMP-1, MMP-3, MMP-12 and CCL20 have previously been reported to be linked with airway diseases, such as COPD and asthma. Furthermore, MAP3K8 regulated the AP-1 transcription factor up-regulation of IL-1β-induced IL-6 and MMP-1 through the ERK1/2 and JNK signaling pathways. MAP3K8 however appears to regulate NF-kB activation through IKKα/β activation independent of the MAPK pathway regulated by itself. In conclusion, MAP3K8 plays a key role in the inflammatory cytokine response post IL-1β stimulation. MAP3K8 gene silencing by siRNA not only suppresses these key inflammatory cytokines but also enhances the therapeutic effect of steroids. MAP3K8 inhibitors might therefore provide a new therapeutic strategy for airway inflammation

Evaluation of Wood Quality of Taiwania Trees Grown with Different Thinning and Pruning Treatments Using Ultrasonic-Wave Testing

The variations of Vtree, Vlumber, MOEtree, and MOElumber in the thinning and pruning treatments showed the similar trend. Results of this study also demonstrate that the effect of silvicultural practices on wood properties can be identified with the ultrasonic-wave properties of trees. This indicates that this non-destructive ultrasonic-wave technique can be provided basic information for future management practice and wood utilization of Taiwania

Crushing Strength Sampling With Minimal Damage to Taiwania (Taiwania Cryptomerioides) Using a Fractometer

The Fractometer is a device that stresses radial increment cores in the direction of the fiber to measure crushing strength, which can provide a direct wood quality indicator for structural lumber. This study analyzes the pattern of the radial variation in Taiwania (Taiwania cryptomerioides Hay.) trunk wood crushing strength to explore its effect on the precision and efficiency of the sampling procedure in the outer increment core zone as an alternate nondestructive sampling method. A pith-to-bark 0.5-cm caliber core was extracted at breast height (1.3 m above the ground) from each tree and was separated into individual section groups. Then individual crushing strengths were determined using the Fractometer.In this study, the variation in crushing strength in the transverse direction increased from the pith outward to the bark side. An analysis of variance and correlation analysis were used to evaluate the data. The magnitude of the radial variation in crushing strength was smaller than the tree-to-tree variation. Including samples of at least 7.2 cm, 5.4 cm, and 2.4 cm near the bark side was found to be acceptable for the assessment of wood crushing strength for trees of Type A (DBH > 27 cm), Type B (DBH = 23~27 cm), and Type C (DBH > 23 cm), respectively

Effect of Moisture Content on the Drill Resistance Value in Taiwania Plantation Wood

The effect of moisture content (MC) on the drill resistance values during desorption from a watersaturated condition of Taiwania (Taiwania cryptomerioides Hayta) plantation lumber was examined. Results showed that the drill resistance values tended to decrease with the decreasing of MC. Positive significant relationships were found among the MC, bulk density, and drill resistance values. This adjustment of density profiles could help the RESISTOGRAPH® to achieve a better measurement of the drill resistance profile of standing trees

Img2Logo:Generating Golden Ratio Logos from Images

Logos are one of the most important graphic design forms that use an abstracted shape to clearly represent the spirit of a community. Among various styles of abstraction, a particular golden-ratio design is frequently employed by designers to create a concise and regular logo. In this context, designers utilize a set of circular arcs with golden ratios (i.e., all arcs are taken from circles whose radii form a geometric series based on the golden ratio) as the design elements to manually approximate a target shape. This error-prone process requires a large amount of time and effort, posing a significant challenge for design space exploration. In this work, we present a novel computational framework that can automatically generate golden ratio logo abstractions from an input image. Our framework is based on a set of carefully identified design principles and a constrained optimization formulation respecting these principles. We also propose a progressive approach that can efficiently solve the optimization problem, resulting in a sequence of abstractions that approximate the input at decreasing levels of detail. We evaluate our work by testing on images with different formats including real photos, clip arts, and line drawings. We also extensively validate the key components and compare our results with manual results by designers to demonstrate the effectiveness of our framework. Moreover, our framework can largely benefit design space exploration via easy specification of design parameters such as abstraction levels, golden circle sizes, etc

RhoGDIβ-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK

We found that overexpression of RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIβ expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIβ physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIβ functions. Moreover, the ZAK-RhoGDIβ interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIβ functions through phosphorylation and RhoGDIβ counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDIβ

ZAK negatively regulates RhoGDIβ-induced Rac1-mediated hypertrophic growth and cell migration

RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIβ plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIβ expression by RNA interference blocked RhoGDIβ-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIβ in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIβ

Flux tunable graphene-based superconducting quantum circuits coupled to 3D cavity

Correlation between transmon and its composite Josephson junctions (JJ) plays an important role in designing new types of superconducting qubits based on quantum materials. It is desirable to have a type of device that not only allows exploration for use in quantum information processing but also probing intrinsic properties in the composite JJs. Here, we construct a flux-tunable 3D transmon-type superconducting quantum circuit made of graphene as a proof-of-concept prototype device. This 3D transmon-type device not only enables coupling to 3D cavities for microwave probes but also permits DC transport measurements on the same device, providing useful connections between transmon properties and critical currents associated with JJ's properties. We have demonstrated how flux-modulation in cavity frequency and DC critical current can be correlated under the influence of Fraunhofer pattern of JJs in an asymmetric SQUID. The correlation analysis was further extended to link the flux-modulated transmon properties, such as flux-tunability in qubit and cavity frequencies, with SQUID symmetry analysis based on DC measurements. Our study paves the way towards integrating novel materials for exploration of new types of quantum devices for future technology while probing underlying physics in the composite materials

Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin

Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine

Initial Presentations Predict Mortality in Pulmonary Tuberculosis Patients - A Prospective Observational Study

Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy.This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated.A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03–1.05), malignancy (RR = 2.42, 95%CI: 1.77–3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12–2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47–0.84), fever (RR = 1.45, 95%CI: 1.09–1.94), and anorexia (RR = 1.49, 95%CI: 1.07–2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p<0.001), anorexia (p = 0.005), and without chronic cough (p<0.001). Among patients of mortality, those with respiratory symptoms of chronic cough (RR = 0.56, 95%CI: 0.33–0.98) and dyspnea (HR = 0.51, 95%CI: 0.27–0.98) were less likely to experience early mortality. The radiological features were comparable between survivors and non-survivors.In addition to demographic characteristics, clinical presentations including the presence of fever, anorexia, and the absence of chronic cough, were also independent predictors for on-treatment mortality in pulmonary tuberculosis patients