Intermediate Network Research Articles

FTA (A Study on Japan's FTA Strategy and its Policy Implications for Korea)

FTA (A Study on Japan's FTA Strategy and its Policy Implications for Korea)

AMPK—friend or foe for targeted therapy?

AMP-activated protein kinase (AMPK) consists of a catalytic α subunit and regulatory β and γ subunits, and is activated in response to an increase in the AMP/ATP ratio upon metabolic stresses. Two AMPK kinases have been identified to mediate activating phosphorylation of AMPKα at Thr172, namely liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) [reviewed in 1]. Increased AMP:ATP can activate AMPK allosterically by binding to the AMPKγ subunit and inhibiting dephosphorylation of Thr172 due to constitutive LKB1 activity. In cells expressing CaMKKβ, increased intracellular Ca2+ concentrations activate AMPK independent of changes in AMP:ATP. Once activated, AMPK phosphorylates multiple downstream catabolic targets that promote ATP generation, whereas anabolic processes including fatty acid synthesis and protein translation tend to be suppressed.1 During tumorigenesis and related depletion of cellular energy, AMPK activation is thought to favor energy-producing catabolic processes. The role of AMPK in prostate cancer (PC) remains to be fully characterized, with significant discrepancies in the literature. We have recently observed that AMPK Thr172 phosphorylation was significantly elevated in human prostate cancer (PC) cells and clinical PC samples. In clinical PC, while not statistically significant, there was a trend for increasing phospho-AMPK Thr172 with increasing Gleason sum score (or increasingly less differentiated disease). The increased AMPK Thr172 phosphoryation was associated with phosphorylation of the AMPK substrate, acetyl CoA-carboxylase (ACC; p = 0.0023), suggesting enhanced AMPK and inhibited ACC activities in PC.2 These findings support earlier reports of increased phospho-ACC levels in clinical PC.3 Functional significance of the observed upregulation of AMPK/ACC status in PC progression remains unclear. In DU145 cells, an androgen receptor (AR) negative human PC line with activated Akt and upregulated glycolysis, 5-aminoimidazole-4-carboxamide riboside (AICAR)-mediated AMPK activation has been reported to suppress proliferation without evidence of increased apoptosis.4 Our recent comparative analysis of the paired PC3 and PC3M cells as models of progressively invasive (androgen-independent) PC also supported the notion of tumor suppressing effects upon activation of AMPK (Fig. 1). Treatment with AICAR or an alternative direct AMPK activator, A-769662 suppressed proliferation, migration and invasion in both cell lines, with down-regulation of mTOR and P70S6Ki levels regardless of the Akt status. Involvement of AMPK was confirmed with the AMPK inhibitor, Compound C and siRNA-mediated AMPK silencing.2 Figure 1. A schematic representation of signaling network involving AMPK and other key signaling nodes in prostate carcinogenesis. The AMPK-mediated anti-tumor effects (proliferative/migratory/invasive) are considered downstream of fatty acid and protein synthesis. ... Despite similar functional responses in PC3 and PC3M cells, AMPK activation also resulted in sustained phospho-Akt activation in PC3M cells, but not PC3 cells. However, combining LY-294002 with AICAR to simultaneously suppress phosphatidylinositol 3′-kinase (PI3K) and activate AMPK did not produce any additional anti-proliferative effects in PC3M cells. This suggests that any efforts to exploit AMPK as a potential therapeutic target may be considered independent of PI3K/Akt signaling. This is a surprising finding as there is significant evidence for cross talk between AMPK and AKT/mTOR pathways. Indeed, the PI3K signaling network exhibits extensive cross-regulatory interactions with the intermediate metabolism network, including AMPK, to fuel resistance to stress and uncontrolled growth.5 Akt has also been reported to dramatically reduce the AMP/ATP ratio and suppress AMPK activity in cells overexpressing a constitutive Akt mutant.6 Hence, while the effects of AMPK activation was not influenced by a PI3K inhibitor in our study, this may be context and cell type specific, and a detailed understanding of AMPK/PI3K/mTOR crosstalk will have important implications in cancer therapies. Popovics et al.7 have recently hypothesized that AMPK activators used in pre-clinical studies are likely to promote autophagy and apoptosis since they mediate their effects, at least in part, by an inhibitory action on the mTORC1 complex. They proposed that modulators of the CaMKKβ-AMPK pathway may be used in combination with mTOR-specific inhibitors, such as the rapamycin analogs, to maximise anti-tumor effects, thus avoiding the the potential of stimulating diverse pro-tumor processes in parallel with antitumor effects when mTOR inhibitor is used alone. Ongoing research into the role of AMPK in the followings research priorities will provide important insight into its potential for targeted therapy: (1) The in vivo impact of AMPK-mediated signaling in the context of primary and metastatic diseases; (2) The complex interplay between CAMKKβ, androgen receptor and AMPK (Fig. 1); (3) Factors that modulate AMPK-induced effects on cell fate (including survival, apoptosis and autophagy) and motility; and (4) Factors influencing the metabolic consequences of AMPK functions, including glucose and lipid metabolism.

Simultaneity Analysis In A Wireless Sensor Network

Abstract An original wireless sensor network for vibration measurements was designed. Its primary purpose is modal analysis of vibrations of large structures. A number of experiments have been performed to evaluate the system, with special emphasis on the influence of different effects on simultaneity of data acquired from remote nodes, which is essential for modal analysis. One of the issues is that quartz crystal oscillators, which provide time reading on the devices, are optimized for use in the room temperature and exhibit significant frequency variations if operated outside the 20–30°C range. Although much research was performed to optimize algorithms of synchronization in wireless networks, the subject of temperature fluctuations was not investigated and discussed in proportion to its significance. This paper describes methods used to evaluate data simultaneity and some algorithms suitable for its improvement in small to intermediate size ad-hoc wireless sensor networks exposed to varying temperatures often present in on-site civil engineering measurements.

Analysis of the Contrasting Pathogenicities Induced by the D222G Mutation in 1918 and 2009 Pandemic Influenza A Viruses.

In 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not compromise binding to human α2,6-linked glycan receptors, allowing it to transmit efficiently. Here we investigate the interconversion mechanism between two predicted binding modes in both 2009 and 1918 HAs, introducing a highly parallel intermediate network search scheme to construct kinetically relevant pathways efficiently. Accumulated mutations at positions 183 and 224 that alter the size of the binding pocket are identified with the fitness of the 2009 pandemic virus carrying the D222G mutation. This result suggests that the pandemic H1N1 viruses could gain binding affinity to the α2,3-linked glycan receptors in the lungs, usually associated with highly pathogenic avian influenza, without compromising viability.

Evolution of bow-tie architectures in biology.

Bow-tie or hourglass structure is a common architectural feature found in many biological systems. A bow-tie in a multi-layered structure occurs when intermediate layers have much fewer components than the input and output layers. Examples include metabolism where a handful of building blocks mediate between multiple input nutrients and multiple output biomass components, and signaling networks where information from numerous receptor types passes through a small set of signaling pathways to regulate multiple output genes. Little is known, however, about how bow-tie architectures evolve. Here, we address the evolution of bow-tie architectures using simulations of multi-layered systems evolving to fulfill a given input-output goal. We find that bow-ties spontaneously evolve when the information in the evolutionary goal can be compressed. Mathematically speaking, bow-ties evolve when the rank of the input-output matrix describing the evolutionary goal is deficient. The maximal compression possible (the rank of the goal) determines the size of the narrowest part of the network—that is the bow-tie. A further requirement is that a process is active to reduce the number of links in the network, such as product-rule mutations, otherwise a non-bow-tie solution is found in the evolutionary simulations. This offers a mechanism to understand a common architectural principle of biological systems, and a way to quantitate the effective rank of the goals under which they evolved.

Specifics of Legal Relations in the Use of Intermediate Heat Networks

Specifics of Legal Relations in the Use of Intermediate Heat Networks

On error detection of intermediate nodes offour-node network with small downstream links

We investigate the error detection ability of intermediate nodes of zig-zag network with small downstream link. We show that the error detection capability of zig-zag networks in the presence of z malicious edges and 2z-1 limited links from node B to node u. Also, at last we analyze a family of networks, which shows that the upper bound of network is smaller than the bound we expected, indicating that Singleton bound is not the tightest bound in the particular condition of network. According to this result, we design corresponding encode and decode strategy to reach the bound we propose in this paper.

METRO: Measurement of End-to-End Route Trust

Given the current situation on the Internet, it is important to determine the trust of the communication routes between a client and server. Such determination can only be established by end terminals such as clients and servers, not by intermediate routers or network providers so far. The revelations regarding PRISM and other programs highlight the importance of this issue. In this paper, a method to identify the trust level of a route between a client and a server is proposed. This method identifies the trust level using packet authentication, Probabilistic Packet Marking (PPM), and knowledge bases maintained by trusted third parties. A prototype system of the proposed method was developed and evaluated, and the evaluation results prove its feasibility. To the best of our knowledge, the proposed method is the first method to identify the trust level of a route based on information obtained from intermediate routers or Autonomous Systems (ASs).

Production network positions, innovation orientation and environmental dynamics: an empirical analysis of Chinese firms

In recent years, local Chinese firms have begun to join global production networks and leverage their local network to enlarge their manufacturing industry. As Chinese firms expand their production networks, their performance may improve due to their innovative use of such networks to diffuse information/knowledge. However, a survey of 171 Chinese firms found that simultaneously pursuing both central and intermediate network positions creates conflict even though both positions positively affect performance. Innovation orientation and environmental dynamics are the areas in which network position affects performance. In highly dynamic environments and for firms with innovation orientations, an intermediate position can improve performance. Conversely, central positions can improve performance for high innovation orientations in less dynamic environments. These results indicate that firms should consider the fitness of the various network positions, innovation strategies and environmental dynamics when expanding their production networks.

Making cultural tourism networks work - the role of collective actors

Culture and tourism have a complementary and mutually beneficial relationship: value offerings are co-created by integrated value chains and networks of interdependent actors. However, building and maintaining cultural tourism networks is far from straightforward: both the tourism industry and the cultural sector are fragmented and heterogeneous, and often seem to be speaking different languages. We investigate how collective actors can contribute to fostering collaborative strategies, focusing on a specific inter-organizational network located in the city of Venice. Our main findings have implications both for managerial and public policies: the identification of actors, positioned at intermediate network levels, who can influence a network’s functioning allows for interventions not generally addressed to the destination as a whole but aimed at solving specific network’s weaknesses. Le produzioni turistiche e culturali sono caratterizzate da una relazione di complementarieta: i processi di creazione del valore si sostanziano in catene del valore integrate e reti di attori interdipendenti. Nonostante cio, la costruzione e il mantenimento delle reti turistico-culturali e tutt’altro che scontata: le produzioni turistiche e culturali sono frammentate ed eterogenee, e spesso sembrano parlare lingue diverse. Il presente lavoro di ricerca analizza come gli attori collettivi possano contribuire allo sviluppo di strategie collaborative, e in particolare si focalizza su un caso di rete inter-organizzativa sviluppata nella citta di Venezia. I principali risultati di questo lavoro hanno implicazioni sia manageriali che di politiche pubbliche: l’identificazione degli attori, posizionati a livelli intermedi della rete, in grado di influenzarne il funzionamento permette di individuare interventi non diretti alla destinazione nel suo insieme, ma volti a risolvere le specifiche debolezze della rete.

Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier

Keratins are cytoskeletal intermediate filament proteins that are increasingly being recognised for their diverse cellular functions. Here we report the consequences of germ line inactivation of Keratin 76 (Krt76) in mice. Homozygous disruption of this epidermally expressed gene causes neonatal skin flaking, hyperpigmentation, inflammation, impaired wound healing, and death prior to 12 weeks of age. We show that this phenotype is associated with functionally defective tight junctions that are characterised by mislocalization of the integral protein CLDN1. We further demonstrate that KRT76 interacts with CLDN1 and propose that this interaction is necessary to correctly position CLDN1 in tight junctions. The mislocalization of CLDN1 has been associated in various dermopathies, including the inflammatory disease, psoriasis. These observations establish a previously unknown connection between the intermediate filament cytoskeleton network and tight junctions and showcase Krt76 null mice as a possible model to study aberrant tight junction driven skin diseases.

Heat exchanger network design of large-scale industrial site with layout inspired constraints

This paper presents a systematic approach for the synthesis of the heat recovery network in total site using a Mixed Integer Linear Programming model. This model returns a near-to-optimal network configuration with minimum utility cost while allows to select geographically closest matches. The Heat Load Distribution is the subproblem of the network design and has been reported to be quite expensive to solve for large-scale problems. The computational complexity of HLD resides in the number of streams and the feasible networks. An additional challenge, raising particularly in industrial problems, has been the intermediate heat transfer network which aggravates the combinatorial complexity. The presented methodology deals with those difficulties by priority consideration based on the location of process units. It helps significantly reducing the computational time and also comes with a realistic network sketch with respect to the plant layout. Several examples are discussed along with a real industrial case study.

Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.

In multicellular organisms, genetic programs guide cells to adopt cell fates as tissues are formed during development, maintained in adults, and repaired after injury. Here we explore how a small molecule in the environment can switch a genetic program from one fate to another. Wild-type Caenorhabditis elegans XX adult hermaphrodites make oocytes continuously, but certain mutant XX adults make sperm instead in an otherwise hermaphrodite soma. Thus, puf-8; lip-1 XX adults make only sperm, but they can be switched from sperm to oocyte production by treatment with a small-molecule MEK inhibitor. To ask whether this chemical reprogramming is common, we tested six XX sperm-only mutants, but found only one other capable of cell fate switching, fbf-1; lip-1. Therefore, reprogramming competence relies on genotype, with only certain mutants capable of responding to the MEK inhibitor with a cell fate change. To gain insight into the molecular basis of competence for chemical reprogramming, we compared polyadenylated transcriptomes of competent and noncompetent XX sperm-only mutants in the absence of the MEK inhibitor and hence in the absence of cell fate reprogramming. Despite their cellular production of sperm, competent mutants were enriched for oogenic messenger RNAs relative to mutants lacking competence for chemical reprogramming. In addition, competent mutants expressed the oocyte-specific protein RME-2, whereas those lacking competence did not. Therefore, mutants competent for reprogramming possess an intersexual molecular profile at both RNA and protein levels. We suggest that this intersexual molecular signature is diagnostic of an intermediate network state that poises the germline tissue for changing its cellular fate in response to environmental cues.

Network Coding-Aware Queue Management for TCP Flows Over Coded Wireless Networks

In this paper, we are interested in improving the performance of TCP flows over wireless networks with a given constructive intersession network coding scheme. We are motivated by the observation that TCP does not fully exploit the potential of the underlying network coding opportunities. In order to improve the performance of TCP flows over coded wireless networks, without introducing changes to TCP itself, we propose a network-coding aware queue management scheme (NCAQM) that is implemented at intermediate network coding nodes and bridges the gap between network coding and TCP rate control. The design of NCAQM is grounded on the network utility maximization (NUM) framework and includes the following mechanisms. NCAQM: 1) stores coded packets at intermediate nodes in order to use the buffer space more efficiently; 2) determines what fraction of the flows should be coded together; and 3) drops packets at intermediate nodes so that it matches the rates of parts of different TCP flows that are coded together. We demonstrate, via simulation, that NCAQM significantly improves TCP throughput compared to TCP over baseline queue management schemes.

Trade in intermediate goods and Euro-Med production networks

This paper examines the involvement of North African (NA) countries in regional production networks using a gravity model of trade augmented with imports of intermediate goods. The model is estimated using disaggregated bilateral exports of final and intermediate goods from four NA countries (Algeria, Egypt, Morocco and Tunisia) to OECD countries over the period 1995–2008. A first hypothesis argues that the Euro-Mediterranean process has led to a greater integration of NA countries in regional production networks. A second hypothesis states that manufacturing companies may transfer part of their production process to countries with lower labour costs, thereby generating increasing trade links between intermediate goods. Our results indicate that NA countries have indeed become more integrated in Euro-Mediterranean production networks and that this has a positive impact on trade flows between the two sides of the Mediterranean Sea. We conclude that the increase in exports from NA countries has been mainly channelled through changes in the rules of origin and the increase in imports of intermediate goods.

Delay-Bounded Priority-Driven Resource Allocation for Video Transmission Over Multihop Networks

In this paper we consider the problem of resource allocation for video transmission over mesh networks with delay bound constraints and priority-based packet scheduling. We observe that priority-driven packet scheduling at the intermediate network routers has a direct and significant impact on the queuing behaviors and delay bound violation probabilities of video packets, as well as the overall end-to-end video distortion. Using learning methods, we develop a packet delay bound violation probability model for video transmission over multihop networks with priority-based packet scheduling. With this model, we can successfully predict the probability of packets being dropped due to violation of specified delay bounds. We also observe that the transmission distortion caused by packet drops exhibits a unique exponential behavior with priority-based packet scheduling. With these analysis results, we formulate the resource allocation for multisession video transmission over networks with priority-driven packet scheduling under delay bound constraints as a multiobjective optimization problem. Evolutionary optimization methods based on single- and multiobjective genetic algorithms are proposed to solve the problem and obtain the optimal resource allocation. Extensive experiment results demonstrate the effectiveness of the proposed resource-distortion models and optimization algorithms.

Emergent properties of composite semiflexible biopolymer networks.

The semiflexible polymers filamentous actin (F-actin) and intermediate filaments (IF) both form complex networks within the cell, and together are key determinants of cellular stiffness. While the mechanics of F-actin networks together with stiff microtubules have been characterized, the interplay between F-actin and IF networks is largely unknown, necessitating the study of composite networks using mixtures of semiflexible biopolymers. We employ bulk rheology in a simplified in vitro system to uncover the fundamental mechanical interactions between networks of the 2 semiflexible polymers, F-actin and vimentin IF. Surprisingly, co-polymerization of actin and vimentin can produce composite networks either stronger or weaker than pure F-actin networks. We show that this effect occurs through steric constraints imposed by IF on F-actin during network formation and filament crosslinking, highlighting novel emergent behavior in composite semiflexible networks.

Batched Sparse Codes

Network coding can significantly improve the transmission rate of communication networks with packet loss compared with routing. However, using network coding usually incurs high computational and storage costs in the network devices and terminals. For example, some network coding schemes require the computational and/or storage capacities of an intermediate network node to increase linearly with the number of packets for transmission, making such schemes difficult to be implemented in a router-like device that has only constant computational and storage capacities. In this paper, we introduce BATched Sparse code (BATS code), which enables a digital fountain approach to resolve the above issue. BATS code is a coding scheme that consists of an outer code and an inner code. The outer code is a matrix generation of a fountain code. It works with the inner code that comprises random linear coding at the intermediate network nodes. BATS codes preserve such desirable properties of fountain codes as ratelessness and low encoding/decoding complexity. The computational and storage capacities of the intermediate network nodes required for applying BATS codes are independent of the number of packets for transmission. Almost capacity-achieving BATS code schemes are devised for unicast networks, two-way relay networks, tree networks, a class of three-layer networks, and the butterfly network. For general networks, under different optimization criteria, guaranteed decoding rates for the receiving nodes can be obtained.

Non-data-aided joint bit-rate and modulation format identification for next-generation heterogeneous optical networks

A novel and cost-effective technique for simultaneous bit-rate and modulation format identification (BR-MFI) in next-generation heterogeneous optical networks is proposed. This technique utilizes an artificial neural network (ANN) in conjunction with asynchronous delay-tap plots (ADTPs) to enable low-cost joint BR-MFI at the receivers as well as at the intermediate network nodes without requiring any prior information from the transmitters. The results of numerical simulations demonstrate successful identification of several commonly-used bit-rates and modulation formats with estimation accuracies in excess of 99.7%. The effectiveness of proposed technique under different channel conditions i.e. optical signal-to-noise ratio (OSNR) in the range of 14–28dB, chromatic dispersion (CD) in the range of −500 to 500ps/nm and differential group delay (DGD) in the range of 0–10ps, is investigated and it has been shown that the proposed technique is robust against all these impairments.

Evaluation of the end-to-end TCP performance for vertical handover using intermediate switching network

Most of the traffic in today's network uses the transmission control protocol TCP as the transport layer protocol for reliable end-to-end packet delivery. However, TCP considers packet loss to be the result of network congestion which makes it unsuitable for mobile wireless communication, where sporadic and temporary packet losses are usual due to fading, shadowing, hand-off and other radio effects. During the vertical hand-off between different wireless technologies, the problem of end-to-end connection and reliability management for TCP becomes more severe. Intermediate switching network ISN is an effective framework for vertical handover between the UMTS and the WLAN network. This paper evaluates the performance of TCP over ISN-based framework. The proposed scheme uses a cross layer interaction between the data link and the transport layers to estimate TCP retransmit timeout and congestion window during handover. Simulation results establishes effectiveness of the proposed scheme.