Nemonoxacin (Taigexyn^®): A New Non-Fluorinated Quinolone

Nemonoxacin (Taigexyn®), a novel C-8-methoxy non-fluorinated quinolone, has been approved for use in community-acquired pneumonia (CAP) in Taiwan (2014) and mainland China (2016). The FDA granted nemonoxacin ‘qualified infectious disease product’ and ‘fast-track’ designations for CAP and acute bacterial skin and skin structure infection in December 2013. It possesses a broad spectrum of bactericidal activity against typical and atypical respiratory pathogens. In particular, nemonoxacin has activity against resistant Gram-positive cocci, including penicillin-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. Oral nemonoxacin was compared with oral levofloxacin for efficacy and safety in three randomized, double-blinded, controlled Phase II–III clinical trials for the treatment of CAP. This article will review the microbiological profile of nemonoxacin against respiratory pathogens including S. pneumoniae and S. aureus, and microbiological outcome data from the three Phase II–III studies

Three-Tier Capacity and Traffic Allocation for Core, Edges, and Devices for Mobile Edge Computing

In order to satisfy the 5G requirements of ultra-low latency, mobile edge computing (MEC)-based architecture, composed of three-tier nodes, core, edges, and devices, is proposed. In MEC-based architecture, previous studies focused on the controlplane issue, i.e., how to allocate traffic to be processed at different nodes to meet this ultra-low latency requirement. Also important is how to allocate the capacity to different nodes in the management plane so as to establish a minimal-capacity network. The objectives of this paper is to solve two problems: 1) to allocate the capacity of all nodes in MEC-based architecture so as to provide a minimal-capacity network and 2) to allocate the traffic to satisfy the latency percentage constraint, i.e., at least a percentage of traffic satisfying the latency constraint. In order to achieve these objectives, a two-phase iterative optimization (TPIO) method is proposed to try to optimize capacity and traffic allocation in MEC-based architecture. TPIO iteratively uses two phases to adjust capacity and traffic allocation respectively because they are tightly coupled. In the first phase, using queuing theory calculates the optimal traffic allocation under fixed allocated capacity, while in the second phase, allocated capacity is further reduced under fixed traffic allocation to satisfy the latency percentage constraint. Simulation results show that MEC-based architecture can save about 20.7% of capacity of two-tier architecture. Further, an extra 12.2% capacity must be forfeited when the percentage of satisfying latency is 90%, compared to 50%.This work was supported in part by H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant number 761586), and Ministry of Science and Technology, Taiwan for financially supporting this research under Contract No. MOST 106-2218-E-009-018

A Novel Adaptive Elite-Based Particle Swarm Optimization Applied to VAR Optimization in Electric Power Systems

Particle swarm optimization (PSO) has been successfully applied to solve many practical engineering problems. However, more efficient strategies are needed to coordinate global and local searches in the solution space when the studied problem is extremely nonlinear and highly dimensional. This work proposes a novel adaptive elite-based PSO approach. The adaptive elite strategies involve the following two tasks: (1) appending the mean search to the original approach and (2) pruning/cloning particles. The mean search, leading to stable convergence, helps the iterative process coordinate between the global and local searches. The mean of the particles and standard deviation of the distances between pairs of particles are utilized to prune distant particles. The best particle is cloned and it replaces the pruned distant particles in the elite strategy. To evaluate the performance and generality of the proposed method, four benchmark functions were tested by traditional PSO, chaotic PSO, differential evolution, and genetic algorithm. Finally, a realistic loss minimization problem in an electric power system is studied to show the robustness of the proposed method

Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH 2

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts

Comparison of diffusion-weighted imaging and contrast-enhanced T1-weighted imaging on a single baseline MRI for demonstrating dissemination in time in multiple sclerosis

BACKGROUND: The 2010 Revisions to the McDonald Criteria have established that dissemination in time (DIT) of multiple sclerosis (MS) can be demonstrated by simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions on a single magnetic resonance imaging (MRI). However, gadolinium-based contrast agents (GBCAs) have contraindications. Diffusion-weighted imaging (DWI) can detect diffusion alterations in active inflammatory lesions. The purpose of this study was to investigate if DWI can be an alternative to contrast-enhanced T1-weighted imaging (CE T1WI) for demonstrating DIT in MS. METHODS: We selected patients with clinically definite MS and evaluated their baseline brain MRI. Asymptomatic lesions were identified as either hyperintense or nonhyperintense on DWI and enhancing or nonenhancing on CE T1WI. Fisher’s exact test was performed to determine whether the hyperintensity on DWI was related to the enhancement on CE T1WI (P < 0.05). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the DWI to predict lesion enhancement were calculated. RESULTS: Twenty-two patients with 384 demyelinating lesions that were hyperintense on T2-weighted imaging and more than 3 mm in size were recruited. The diffusion hyperintensity and lesion enhancement were significantly correlated (P <0.001). The sensitivity, specificity, PPV, NPV and accuracy were 100%, 67.9%, 32.3%, 100% and 72.1%, respectively. CONCLUSIONS: A hyperintense DWI finding does not necessarily overlap with contrast enhancement. There are many false positives, possibly representing other stages of lesion development. Although DWI may not replace CE T1WI imaging to demonstrate DIT due to the low PPV, it may serve as a screening MRI sequence where the use of GBCAs is a concern

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Mobile Edge Computing Platform Deployment in 4G LTE Networks: A Middlebox Approach

This paper has been presented at : USENIX Workshop on Hot Topics in Edge Computing (Hot Edge '18)Low-latency demands for cellular networks have at-tracted much attention. Mobile edge computing (MEC), which deploys a cloud computing platform at the edge closer to mobile users, has been introduced as an enabler of low-latency performance in 4G and 5G networks. In this paper, we propose an MEC platform deployment so-lution in 4G LTE networks using a middlebox approach. It is standard-compliant and transparent to existing cel-lular network components, so they need not be modified. The MEC middlebox sits on the S1 interface, which con-nects an LTE base station to its core network, and does traffic filtering, manipulation and forwarding. It enables the MEC service for mobile users by hosting application servers. Such middlebox approach can save deployment cost and be easy to install. It is different from other stud-ies that require modifications on base stations or/and core networks. We have confirmed its viability through a pro-totype based on the OpenAirInterface cellular platform.We thank our shepherd Weisong Shi for his help, and also thank the anonymous reviewers for their valuable comments on improving this paper. This work was partially supported by the Ministry of Science and Technology, Taiwan, under grant numbers 106-2622-8-009-017 and 106-2218-E-009-018, and by the H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant number 761586)

D2ADA: Dynamic Density-aware Active Domain Adaptation for Semantic Segmentation

In the field of domain adaptation, a trade-off exists between the model performance and the number of target domain annotations. Active learning, maximizing model performance with few informative labeled data, comes in handy for such a scenario. In this work, we present D2ADA, a general active domain adaptation framework for semantic segmentation. To adapt the model to the target domain with minimum queried labels, we propose acquiring labels of the samples with high probability density in the target domain yet with low probability density in the source domain, complementary to the existing source domain labeled data. To further facilitate labeling efficiency, we design a dynamic scheduling policy to adjust the labeling budgets between domain exploration and model uncertainty over time. Extensive experiments show that our method outperforms existing active learning and domain adaptation baselines on two benchmarks, GTA5 -> Cityscapes and SYNTHIA -> Cityscapes. With less than 5% target domain annotations, our method reaches comparable results with that of full supervision.Comment: 14 pages, 5 figure