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Sample records for attack complex inhibitor

  1. Supported Lipid Bilayer Platform To Test Inhibitors of the Membrane Attack Complex: Insights into Biomacromolecular Assembly and Regulation.

    Science.gov (United States)

    Yorulmaz, Saziye; Jackman, Joshua A; Hunziker, Walter; Cho, Nam-Joon

    2015-11-01

    Complement activation plays an important role in innate immune defense by triggering formation of the membrane attack complex (MAC), which is a biomacromolecular assembly that exhibits membrane-lytic activity against foreign invaders including various pathogens and biomaterials. Understanding the details of MAC structure and function has been the subject of extensive work involving bulk liposome and erythrocyte assays. However, it is difficult to characterize the mechanism of action of MAC inhibitor drug candidates using the conventional assays. To address this issue, we employ a biomimetic supported lipid bilayer platform to investigate how two MAC inhibitors, vitronectin and clusterin, interfere with MAC assembly in a sequential addition format, as monitored by the quartz crystal microbalance-dissipation (QCM-D) technique. Two experimental strategies based on modular assembly were selected, precincubation of inhibitor and C5b-7 complex before addition to the lipid bilayer or initial addition of inhibitor followed by the C5b-7 complex. The findings indicate that vitronectin inhibits membrane association of C5b-7 via a direct interaction with C5b-7 and via competitive membrane association onto the supported lipid bilayer. On the other hand, clusterin directly interacts with C5b-7 such that C5b-7 is still able to bind to the lipid bilayer, and clusterin affects the subsequent binding of other complement proteins involved in the MAC assembly. Taken together, the findings in this study outline a biomimetic approach based on supported lipid bilayers to explore the interactions between complement proteins and inhibitors, thereby offering insight into MAC assembly and regulation.

  2. Percolation of localized attack on complex networks

    CERN Document Server

    Shao, Shuai; Stanley, H Eugene; Havlin, Shlomo

    2014-01-01

    The robustness of complex networks against node failure and malicious attack has been of interest for decades, while most of the research has focused on random attack or hub-targeted attack. In many real-world scenarios, however, attacks are neither random nor hub-targeted, but localized, where a group of neighboring nodes in a network are attacked and fail. In this paper we develop a percolation framework to analytically and numerically study the robustness of complex networks against such localized attack. In particular, we investigate this robustness in Erd\\H{o}s-R\\'{e}nyi networks, random-regular networks, and scale-free networks. Our results provide insight into how to better protect networks, enhance cybersecurity, and facilitate the design of more robust infrastructures.

  3. Detection of complex cyber attacks

    Science.gov (United States)

    Gregorio-de Souza, Ian; Berk, Vincent H.; Giani, Annarita; Bakos, George; Bates, Marion; Cybenko, George; Madory, Doug

    2006-05-01

    One significant drawback to currently available security products is their inabilty to correlate diverse sensor input. For instance, by only using network intrusion detection data, a root kit installed through a weak username-password combination may go unnoticed. Similarly, an administrator may never make the link between deteriorating response times from the database server and an attacker exfiltrating trusted data, if these facts aren't presented together. Current Security Information Management Systems (SIMS) can collect and represent diverse data but lack sufficient correlation algorithms. By using a Process Query System, we were able to quickly bring together data flowing from many sources, including NIDS, HIDS, server logs, CPU load and memory usage, etc. We constructed PQS models that describe dynamic behavior of complicated attacks and failures, allowing us to detect and differentiate simultaneous sophisticated attacks on a target network. In this paper, we discuss the benefits of implementing such a multistage cyber attack detection system using PQS. We focus on how data from multiple sources can be combined and used to detect and track comprehensive network security events that go unnoticed using conventional tools.

  4. Longest-path attacks on complex networks

    CERN Document Server

    Pu, Cunlai

    2014-01-01

    We investigate the longest-path attacks on complex networks. Specifically, we remove approximately the longest simple path from a network iteratively until there are no paths left in the network. We propose two algorithms, the random augmenting approach (RPA) and the Hamilton-path based approach (HPA), for finding the approximately longest simple path in a network. Results demonstrate that steps of longest-path attacks increase with network density linearly for random networks, while exponentially increasing for scale-free networks. The more homogeneous the degree distribution is, the more fragile the network, which is totally different from the previous results of node or edge attacks. HPA is generally more efficient than RPA in the longest-path attacks of complex networks. These findings further help us understand the vulnerability of complex systems, better protect complex systems, and design more tolerant complex systems.

  5. The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly.

    Science.gov (United States)

    Escudero-Esparza, Astrid; Kalchishkova, Nikolina; Kurbasic, Emila; Jiang, Wen G; Blom, Anna M

    2013-12-01

    CUB and Sushi multiple domains 1 (CSMD1) is a transmembrane protein containing 15 consecutive complement control protein (CCP) domains, which are characteristic for complement inhibitors. We expressed a membrane-bound fragment of human CSMD1 composed of the 15 C-terminal CCP domains and demonstrated that it inhibits deposition of C3b by the classical pathway on the surface of Chinese hamster ovary cells by 70% at 6% serum and of C9 (component of membrane attack complex) by 90% at 1.25% serum. Furthermore, this fragment of CSMD1 served as a cofactor to factor I-mediated degradation of C3b. In all functional assays performed, well-characterized complement inhibitors were used as positive controls, whereas Coxsackie adenovirus receptor, a protein with no effect on complement, was a negative control. Moreover, attenuation of expression in human T47 breast cancer cells that express endogenous CSMD1 significantly increased C3b deposition on these cells by 45% at 8% serum compared with that for the controls. Furthermore, by expressing a soluble 17-21 CCP fragment of CSMD1, we found that CSMD1 inhibits complement by promoting factor I-mediated C4b/C3b degradation and inhibition of MAC assembly at the level of C7. Our results revealed a novel complement inhibitor for the classical and lectin pathways. PMID:23964079

  6. Correlations in complex networks under attack

    CERN Document Server

    Srivastava, Animesh; Ganguly, Niloy; Peruani, Fernando; 10.1103/PhysRevE.86.036106

    2013-01-01

    For any initial correlated network after any kind of attack where either nodes or edges are removed, we obtain general expressions for the degree-degree probability matrix and degree distribution. We show that the proposed analytical approach predicts the correct topological changes after the attack by comparing the evolution of the assortativity coefficient for different attack strategies and intensities in theory and simulations. We find that it is possible to turn an initial assortative network into a disassortative one, and vice versa, by fine-tuning removal of either nodes or edges. For an initial uncorrelated network, on the other hand, we discover that only a targeted edge-removal attack can induce such correlations.

  7. Robustness of Complex Networks under Attack and Repair

    Institute of Scientific and Technical Information of China (English)

    HU Bin; LI Fang; ZHOU Hou-Shun

    2009-01-01

    To study the robustness of complex networks under attack and repair,we introduce a repair model of complex networks.Based on the model,we introduce two new quantities,i.e.attack fraction f_a and the maximum degree of the nodes that have never been attacked K_a,to study analytically the critical attack fraction and the relati ve size of the giant component of complex networks under attack and repair,using the method of generating function.We show analytically and numerically that the repair strategy significantly enhances the robustness of the scale-free network and the effect of robustness improvement is better for the scale-free networks with a smaller degree exponent.We discuss the application of our theory in relation to the understanding of robustness of complex networks with reparability.

  8. Why cryptography should not rely on physical attack complexity

    CERN Document Server

    Krämer, Juliane

    2015-01-01

    This book presents two practical physical attacks. It shows how attackers can reveal the secret key of symmetric as well as asymmetric cryptographic algorithms based on these attacks, and presents countermeasures on the software and the hardware level that can help to prevent them in the future. Though their theory has been known for several years now, since neither attack has yet been successfully implemented in practice, they have generally not been considered a serious threat. In short, their physical attack complexity has been overestimated and the implied security threat has been underestimated. First, the book introduces the photonic side channel, which offers not only temporal resolution, but also the highest possible spatial resolution. Due to the high cost of its initial implementation, it has not been taken seriously. The work shows both simple and differential photonic side channel analyses. Then, it presents a fault attack against pairing-based cryptography. Due to the need for at least two indepe...

  9. Recombinant human C1-inhibitor in the treatment of acute angioedema attacks

    NARCIS (Netherlands)

    Choi, Goda; Soeters, Maarten R.; Farkas, Henriette; Varga, Lilian; Obtulowicz, Krystyna; Bilo, Barbara; Porebski, Greg; Hack, C. Erik; Verdonk, Rene; Nuijens, Jan; Levi, Marcel

    2007-01-01

    Background: Patients with hereditary C1-inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1-inhibitor concentrate. A recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the effe

  10. Optimal attack strategy of complex networks based on tabu search

    Science.gov (United States)

    Deng, Ye; Wu, Jun; Tan, Yue-jin

    2016-01-01

    The problem of network disintegration has broad applications and recently has received growing attention, such as network confrontation and disintegration of harmful networks. This paper presents an optimized attack strategy model for complex networks and introduces the tabu search into the network disintegration problem to identify the optimal attack strategy, which is a heuristic optimization algorithm and rarely applied to the study of network robustness. The efficiency of the proposed solution was verified by comparing it with other attack strategies used in various model networks and real-world network. Numerical experiments suggest that our solution can improve the effect of network disintegration and that the "best" choice for node failure attacks can be identified through global searches. Our understanding of the optimal attack strategy may also shed light on a new property of the nodes within network disintegration and deserves additional study.

  11. Vulnerability of complex networks under three-level-tree attacks

    Science.gov (United States)

    Hao, Yao-hui; Han, Ji-hong; Lin, Yi; Liu, Lin

    2016-11-01

    We investigate vulnerability of complex networks including model networks and real world networks subject to three-level-tree attack. Specifically, we remove three different three-level-tree structures: RRN (Random Root Node), MaxDRN (Max Degree Root Node) and MinDRN (Min Degree Root Node) from a network iteratively until there is no three-level-tree left. Results demonstrate that random network is more robust than scale-free network against three tree attacks, and the robustness of random network decreases as the increases. And scale-free network shows different characteristics in different tree attack modes. The robustness of scale-free is not affected by the parameters for RRN, but increases as the increases for MinDRN. The important thing is that MaxDRN is the most effective in the three tree attack modes, especially for scale-free network. These findings supplement and extend the previous attack results on nodes and edges, and can thus help us better explain the vulnerability of different networks, and provide an insight into more tolerant real complex systems design.

  12. Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase

    DEFF Research Database (Denmark)

    Guo, Song; Olesen, Jes; Ashina, Messoud

    2014-01-01

    The initiating mechanisms of migraine attacks are very complex but may involve the cyclic AMP signalling pathway. It is unknown whether intracellular cyclic AMP accumulation induces migraine attacks. We investigated whether administration of cilostazol, which causes cyclic AMP accumulation, may i...

  13. Managing Complex Battlespace Environments Using Attack the Network Methodologies

    DEFF Research Database (Denmark)

    Mitchell, Dr. William L.

    This paper examines the last 8 years of development and application of Attack the Network (AtN) intelligence methodologies for creating shared situational understanding of complex battlespace environment and the development of deliberate targeting frameworks. It will present a short history...... of their development, how they are integrated into operational planning through strategies of deliberate targeting for modern operations. The paper will draw experience and case studies from Iraq, Syria, and Afghanistan and will offer some lessons learned as well as insight into the future of these methodologies...

  14. Robustness of Complex Networks against Attacks Guided by Damage

    CERN Document Server

    Wang, Hui; Xu, Xiaomin; Xiao, Yanghua; Wang, Wei

    2011-01-01

    Extensive researches have been dedicated to investigating the performance of real networks and synthetic networks against random failures or intentional attack guided by degree (degree attack). Degree is one of straightforward measures to characterize the vitality of a vertex in maintaining the integrity of the network but not the only one. Damage, the decrease of the largest component size that was caused by the removal of a vertex, intuitively is a more destructive guide for intentional attack on networks since the network functionality is usually measured by the largest component size. However, it is surprising to find that little is known about behaviors of real networks or synthetic networks against intentional attack guided by damage (damage attack), in which adversaries always choose the vertex with the largest damage to attack. In this article, we dedicate our efforts to understanding damage attack and behaviors of real networks as well as synthetic networks against this attack. To this end, existing ...

  15. Analysis and visualization of large complex attack graphs for networks security

    Science.gov (United States)

    Chen, Hongda; Chen, Genshe; Blasch, Erik; Kruger, Martin; Sityar, Irma

    2007-04-01

    In this paper, we have proposed a comprehensive and innovative approach for analysis and visualization of large complex multi-step cyber attack graphs. As an automated tool for cyber attack detection, prediction, and visualization, the newly proposed method transforms large quantities of network security data into real-time actionable intelligence, which can be used to (1) provide guidance on network hardening to prevent attacks, (2) perform real-time attack event correlation during active attacks, and (3) formulate post-attack responses. We show that it is possible to visualize the complex graphs, including all possible network attack paths while still keeping complexity manageable. The proposed analysis and visualization tool provides an efficient and effective solution for predicting potential attacks upon observed intrusion evidence, as well as interactive multi-resolution views such that an analyst can first obtain high-level overviews quickly, and then drill down to specific details.

  16. Structural basis of complement membrane attack complex formation

    Science.gov (United States)

    Serna, Marina; Giles, Joanna L.; Morgan, B. Paul; Bubeck, Doryen

    2016-02-01

    In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a `multi-hit' mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a `split-washer' configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration.

  17. The dynamic correlation between degree and betweenness of complex network under attack

    Science.gov (United States)

    Nie, Tingyuan; Guo, Zheng; Zhao, Kun; Lu, Zhe-Ming

    2016-09-01

    Complex networks are often subjected to failure and attack. Recent work has addressed the resilience of complex networks to either random or intentional deletion of nodes or links. Here we simulate the breakdown of the small-world network and the scale-free network under node failure or attacks. We analyze and discuss the dynamic correlation between degree and betweenness in the process of attack. The simulation results show that the correlation for scale-free network obeys a power law distribution until the network collapses, while it represents irregularly for small-world network.

  18. Low Complexity Signed Response Based Sybil Attack Detection Mechanism in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    M. Saud Khan

    2016-01-01

    Full Text Available Security is always a major concern in wireless sensor networks (WSNs. Identity based attacks such as spoofing and sybil not only compromise the network but also slow down its performance. This paper proposes a low complexity sybil attack detection scheme, that is, based on signed response (SRES authentication mechanism developed for Global System for Mobile (GSM communications. A probabilistic model is presented which analyzes the proposed authentication mechanism for its probability of sybil attack. The paper also presents a simulation based comparative analysis of the existing sybil attack schemes with respect to the proposed scheme. It is observed that the proposed sybil detection scheme exhibits lesser computational cost and power consumption as compared to the existing schemes for the same sybil detection performance.

  19. C1-inhibitor therapy for hereditary angioedema attacks: prospective patient assessments of health-related quality of life.

    Science.gov (United States)

    Bewtra, Againdra K; Levy, Robyn J; Jacobson, Kraig W; Wasserman, Richard L; Machnig, Thomas; Craig, Timothy J

    2012-01-01

    C1-inhibitor (INH) concentrate, which is recommended as first-line treatment for acute hereditary angioedema (HAE) attacks in many countries, was recently approved in the United States. We sought to solicit patients' feedback about their health-related quality of life (HRQoL) while being treated with C1-INH concentrate for acute HAE attacks under real-world conditions, as well as the personal impact of the availability of C1-INH on lifestyle and mental health domains. Subjects enrolled in an open-label study of C1-INH at 20 U/kg for acute HAE attacks were invited to participate in a prospectively designed survey to solicit "real-time" patient responses that were collected via an interactive voice response service or online with a personal computer. Eighteen subjects submitted 60 quarterly HRQoL and treatment impact survey responses over 29 months. Seventeen of 18 patients responding reported mean short form 12 HRQoL scores that were within a normal range. More than one-half indicated that C1-INH availability made them feel somewhat or much better, and >80% reported having a better outlook on the future and feeling more secure about the danger of life-threatening attacks. These data confirm a high level of HRQoL and a positive impact in lifestyle and emotional domains among patients who were treated for acute attacks of HAE with C1-INH concentrate.

  20. A Robustness Model of Complex Networks with Tunable Attack Information Parameter

    Institute of Scientific and Technical Information of China (English)

    WU Jun; TAN Yue-Jin; DENG Hong-Zhong; LI Yong

    2007-01-01

    We introduce a novel model for robustness of complex with a tunable attack information parameter. The random failure and intentional attack known are the two extreme cases of our model. Based on the model, we study the robustness of complex networks under random information and preferential information, respectively. Using the generating function method, we derive the exact value of the critical removal fraction of nodes for the disintegration of networks and the size of the giant component. We show that hiding just a small fraction of nodes randomly can prevent a scale-free network from collapsing and detecting just a small fraction of nodes preferentially can destroy a scale-free network.

  1. Efficiency of attack strategies on complex model and real-world networks

    CERN Document Server

    Bellingeri, Michele; Vincenzi, Simone

    2013-01-01

    We investigated the efficiency of attack strategies to network nodes when targeting several complex model and real-world networks. We tested 5 attack strategies, 3 of which were introduced in this work for the first time, to attack 3 model (Erdos and Renyi, Barabasi and Albert preferential attachment network, and scale-free network configuration models) and 3 real networks (Gnutella peer-to-peer network, email network of the University of Rovira i Virgili, and immunoglobulin interaction network). Nodes were removed sequentially according to the importance criterion defined by the attack strategy. We used the size of the largest connected component (LCC) as a measure of network damage. We found that the efficiency of attack strategies (fraction of nodes to be deleted for a given reduction of LCC size) depends on the topology of the network, although attacks based on the number of connections of a node and betweenness centrality were often the most efficient strategies. Sequential deletion of nodes in decreasin...

  2. Heart Attack

    Science.gov (United States)

    ... having another heart attack. These medicines include: aspirin, beta blockers, statins, ACE inhibitors and fish oil. Your doctor ... have had a stent placed in your heart. Beta blockers are a group of drugs that lower the ...

  3. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    OpenAIRE

    Monteiro, L; Bonnemaison, D; Vekris, A. (A.); Petry, K G; Bonnet, J; Vidal, R.; Cabrita, J; Mégraud, F.

    1997-01-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet.

  4. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    Science.gov (United States)

    Monteiro, L; Bonnemaison, D; Vekris, A; Petry, K G; Bonnet, J; Vidal, R; Cabrita, J; Mégraud, F

    1997-04-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet. PMID:9157172

  5. Current topics on inhibitors of respiratory complex I.

    Science.gov (United States)

    Murai, Masatoshi; Miyoshi, Hideto

    2016-07-01

    There are a variety of chemicals which regulate the functions of bacterial and mitochondrial complex I. Some of them, such as rotenone and piericidin A, have been indispensable molecular tools in mechanistic studies on complex I. A large amount of experimental data characterizing the actions of complex I inhibitors has been accumulated so far. Recent X-ray crystallographic structural models of entire complex I may be helpful to carefully interpret this data. We herein focused on recent hot topics on complex I inhibitors and the subjects closely connected to these inhibitors, which may provide useful information not only on the structural and functional aspects of complex I, but also on drug design targeting this enzyme. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.

  6. Bush animal attacks: management of complex injuries in a resource-limited setting

    Directory of Open Access Journals (Sweden)

    Mitchell Katrina B

    2011-12-01

    Full Text Available Abstract Introduction Though animal-related injuries and fatalities have been documented throughout the world, the variety of attacks by wild animals native to rural East Africa are less commonly described. Given the proximity of our northwestern Tanzania hospital to Lake Victoria, Lake Tanganyika, and the Serengeti National Park, and presentation of several patients attacked by bush animals and suffering a variety of complex injuries, we sought to report the pattern of attacks and surgical management in a resource-limited setting. Materials and methods Four patients who were admitted to the northwestern Tanzania tertiary referral hospital, Bugando Medical Centre (BMC, in 2010-2011 suffered attacks by different bush animals: hyena, elephant, crocodile, and vervet monkey. These patients were triaged as trauma patients in the Casualty Ward, then admitted for inpatient monitoring and treatment. Their outcomes were followed to discharge. Results The age and gender of the patients attacked was variable, though all but the pediatric patient were participating in food gathering or guarding activities in rural locations at the time of the attacks. All patients required surgical management of their injuries, which included debridement and closure of wounds, chest tube insertion, amputation, and external fixation of an extremity fracture. All patients survived and were discharged home. Discussion Though human injuries secondary to encounters with undomesticated animals such as cows, moose, and camel are reported, they often are indirect traumas resulting from road traffic collisions. Snake attacks are well documented and common. However, this series of unique bush animal attacks describes the initial and surgical management of human injuries in the resource-limited setting of the developing world. Conclusion Animal attacks are common throughout the world, but their pattern may vary in Africa throughout jungle and bush environmental settings. It is

  7. Angioedema Related to Angiotensin-Converting Enzyme Inhibitors: Attack Severity, Treatment, and Hospital Admission in a Prospective Multicenter Study.

    Science.gov (United States)

    Javaud, Nicolas; Achamlal, Jallal; Reuter, Paul-George; Lapostolle, Frédéric; Lekouara, Akim; Youssef, Mustapha; Hamza, Lilia; Karami, Ahmed; Adnet, Frédéric; Fain, Olivier

    2015-11-01

    The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack.A prospective, multicenter, observational study (April 2012-December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission.Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5-1.0] versus 3.9 [2.5-7.0] hours; P patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3-28.2] and 5.9 [1.3-26.5], respectively). A favorable course was observed in all patients. Three patients (5%) experienced a recurrence after angiotensin-converting enzyme inhibitor discontinuation after a median follow-up of 18 (11-30) months.Two severity criteria-laryngeal edema and the progression of the edema-were independent factors associated with

  8. Identifying Vulnerable Nodes of Complex Networks in Cascading Failures Induced by Node-Based Attacks

    Directory of Open Access Journals (Sweden)

    Shudong Li

    2013-01-01

    Full Text Available In the research on network security, distinguishing the vulnerable components of networks is very important for protecting infrastructures systems. Here, we probe how to identify the vulnerable nodes of complex networks in cascading failures, which was ignored before. Concerned with random attack (RA and highest load attack (HL on nodes, we model cascading dynamics of complex networks. Then, we introduce four kinds of weighting methods to characterize the nodes of networks including Barabási-Albert scale-free networks (SF, Watts-Strogatz small-world networks (WS, Erdos-Renyi random networks (ER, and two real-world networks. The simulations show that, for SF networks under HL attack, the nodes with small value of the fourth kind of weight are the most vulnerable and the ones with small value of the third weight are also vulnerable. Also, the real-world autonomous system with power-law distribution verifies these findings. Moreover, for WS and ER networks under both RA and HL attack, when the nodes have low tolerant ability, the ones with small value of the fourth kind of weight are more vulnerable and also the ones with high degree are easier to break down. The results give us important theoretical basis for digging the potential safety loophole and making protection strategy.

  9. Octahedral ruthenium complexes as protein kinase inhibitors

    OpenAIRE

    Li FENG

    2010-01-01

    Die vorliegende Arbeit beschäftigt sich mit einer Strategie zur Darstellung von selektiven Proteinkinaseinhibitoren unter Verwendung starrer, oktaedrischer Rutheniumkomplexe als Strukturmerkmal. Nanomolare Inhibitoren für die Proteinkinasen PAK1, MLCK und DAPK1, sowie ein picomolarer Inhibitor für die Proteinkinase Pim1 wurden entwickelt. Diese Inhibitoren weisen eine außerordentlich hohe Selektivität gegenüber den anderen ...

  10. Effect of the selective serotonin reuptake inhibitor fluvoxamine on CCK-4 induced panic attacks

    NARCIS (Netherlands)

    vanMegen, HJGM; Westenberg, HGM; denBoer, JA; Slaap, B; Scheepmakers, A

    1997-01-01

    Data from animal studies suggest a functional relationship between the cholecystokinin-ergic (CCK) and the serotonergic (5-HT) system. There is increasing evidence that the cholecystokinin-4 (CCK4) challenge test could be a valid experimental model for panic attacks in man. The aim of the present st

  11. Building Damage-Resilient Dominating Sets in Complex Networks against Random and Targeted Attacks

    CERN Document Server

    Molnar, F; Szymanski, B K; Korniss, G

    2014-01-01

    We study the vulnerability of dominating sets against random and targeted node removals in complex networks. While small, cost-efficient dominating sets play a significant role in controllability and observability of these networks, a fixed and intact network structure is always implicitly assumed. We find that cost-efficiency of dominating sets optimized for small size alone comes at a price of being vulnerable to damage; domination in the remaining network can be severely disrupted, even if a small fraction of dominator nodes are lost. We develop two new methods for finding flexible dominating sets, allowing either adjustable overall resilience, or dominating set size, while maximizing the dominated fraction of the remaining network after the attack. We analyze the efficiency of each method on synthetic scale-free networks, as well as real complex networks.

  12. Structure of the poly-C9 component of the complement membrane attack complex

    Science.gov (United States)

    Dudkina, Natalya V.; Spicer, Bradley A.; Reboul, Cyril F.; Conroy, Paul J.; Lukoyanova, Natalya; Elmlund, Hans; Law, Ruby H. P.; Ekkel, Susan M.; Kondos, Stephanie C.; Goode, Robert J. A.; Ramm, Georg; Whisstock, James C.; Saibil, Helen R.; Dunstone, Michelle A.

    2016-02-01

    The membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major component of the MAC, a multi-protein complex that forms pores in the membrane of target pathogens. In contrast to homologous proteins such as perforin and the cholesterol-dependent cytolysins (CDCs), all of which require the membrane for oligomerisation, C9 assembles directly onto the nascent MAC from solution. However, the molecular mechanism of MAC assembly remains to be understood. Here we present the 8 Å cryo-EM structure of a soluble form of the poly-C9 component of the MAC. These data reveal a 22-fold symmetrical arrangement of C9 molecules that yield an 88-strand pore-forming β-barrel. The N-terminal thrombospondin-1 (TSP1) domain forms an unexpectedly extensive part of the oligomerisation interface, thus likely facilitating solution-based assembly. These TSP1 interactions may also explain how additional C9 subunits can be recruited to the growing MAC subsequent to membrane insertion.

  13. Soluble membrane attack complex is diagnostic for intraventricular shunt infection in children

    Science.gov (United States)

    Ramos, Theresa N.; Arynchyna, Anastasia A.; Blackburn, Tessa E.; Johnston, James M.

    2016-01-01

    BACKGROUND. Children treated with cerebrospinal fluid (CSF) shunts to manage hydrocephalus frequently develop shunt failure and/or infections, conditions that present with overlapping symptoms. The potential life-threatening nature of shunt infections requires rapid diagnosis; however, traditional microbiology is time consuming, expensive, and potentially unreliable. We set out to identify a biomarker that would identify shunt infection. METHODS. CSF was assayed for the soluble membrane attack complex (sMAC) by ELISA in patients with suspected shunt failure or infection. CSF was obtained at the time of initial surgical intervention. Statistical analysis was performed to assess the diagnostic potential of sMAC in pyogenic-infected versus noninfected patients. RESULTS. Children with pyogenic shunt infection had significantly increased sMAC levels compared with noninfected patients (3,211 ± 1,111 ng/ml vs. 26 ± 3.8 ng/ml, P = 0.0001). In infected patients undergoing serial CSF draws, sMAC levels were prognostic for both positive and negative clinical outcomes. Children with delayed, broth-only growth of commensal organisms (P. acnes, S. epidermidis, etc.) had the lowest sMAC levels (7.96 ± 1.7 ng/ml), suggesting contamination rather than shunt infection. CONCLUSION. Elevated CSF sMAC levels are both sensitive and specific for diagnosing pyogenic shunt infection and may serve as a useful prognostic biomarker during recovery from infection. FUNDING. This work was supported in part by the Impact Fund of Children’s of Alabama.

  14. The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes

    DEFF Research Database (Denmark)

    Leslie, Robert Graham Quinton; Nielsen, Claus Henrik

    2004-01-01

    The contributions of the classical (CP) and alternative (AP) pathways of complement activation to the spontaneous deposition of C3 fragments and the formation of membrane attack complexes (MAC) on human B lymphocytes, were assessed by incubating peripheral blood mononuclear cells with autologous...... serum in the absence and presence of selective inhibitors of the AP and CP, respectively. While the total amount of C3 fragments deposited was relatively unaffected by blocking either pathway individually, deposition was virtually abrogated by their combined blockade. A marked difference was observed......, however, in the nature of the fragments deposited as a result of CP and AP activation: C3b fragments deposited via the CP were extensively ( approximately 90%) converted to the terminal degradation product, C3dg, whereas about 50% of those deposited by the AP persisted as C3b/iC3b fragments. The extent of...

  15. $k$-core percolation on complex networks: Comparing random, localized and targeted attacks

    CERN Document Server

    Yuan, Xin; Stanley, H Eugene; Havlin, Shlomo

    2016-01-01

    The type of malicious attack inflicting on networks greatly influences their stability under ordinary percolation in which a node fails when it becomes disconnected from the giant component. Here we study its generalization, $k$-core percolation, in which a node fails when it loses connection to a threshold $k$ number of neighbors. We study and compare analytically and by numerical simulations of $k$-core percolation the stability of networks under random attacks (RA), localized attacks (LA) and targeted attacks (TA), respectively. By mapping a network under LA or TA into an equivalent network under RA, we find that in both single and interdependent networks, TA exerts the greatest damage to the core structure of a network. We also find that for Erd\\H{o}s-R\\'{e}nyi (ER) networks, LA and RA exert equal damage to the core structure whereas for scale-free (SF) networks, LA exerts much more damage than RA does to the core structure.

  16. Not all ACE inhibitor related angioedema is always evident: a case which is misdiagnosed as panic attack and speech disorder.

    Science.gov (United States)

    Gulec, M; Caliskaner, Z; Kartal, O; Erel, F; Karaayvaz, M

    2007-01-01

    Angiotensin-converting enzyme (ACE) inhibitors are the most common medications responsible for angioedema. Angioedema is a potentially life threatening conditions especially in geriatric age patients that they have take a several medications include ACE inhibitors and non steroidal anti inflammatory drugs. We present a case an ACE inhibitor induced angioedema that confused many clinical events. PMID:18047821

  17. Mathematical Attacks on RSA Cryptosystem

    Directory of Open Access Journals (Sweden)

    Imad K. Salah

    2006-01-01

    Full Text Available In this paper some of the most common attacks against Rivest, Shamir, and Adleman (RSA cryptosystem are presented. We describe the integer factoring attacks, attacks on the underlying mathematical function, as well as attacks that exploit details in implementations of the algorithm. Algorithms for each type of attacks are developed and analyzed by their complexity, memory requirements and area of usage.

  18. A Nicotiana attenuata cell wall invertase inhibitor (NaCWII) reduces growth and increases secondary metabolite biosynthesis in herbivore-attacked plants.

    Science.gov (United States)

    Ferrieri, Abigail P; Arce, Carla C M; Machado, Ricardo A R; Meza-Canales, Ivan D; Lima, Eraldo; Baldwin, Ian T; Erb, Matthias

    2015-10-01

    Plant invertases are sucrolytic enzymes that are essential for the regulation of carbohydrate metabolism and source-sink relationships. While their activity has been well documented during abiotic and biotic stresses, the role of proteinaceous invertase inhibitors in regulating these changes is unknown. Here, we identify a putative Nicotiana attenuata cell wall invertase inhibitor (NaCWII) which is strongly up-regulated in a jasmonate (JA)-dependent manner following simulated attack by the specialist herbivore Manduca sexta. To understand the role of NaCWII in planta, we silenced its expression by RNA interference and measured changes in primary and secondary metabolism and plant growth following simulated herbivory. NaCWII-silenced plants displayed a stronger depletion of carbohydrates and a reduced capacity to increase secondary metabolite pools relative to their empty vector control counterparts. This coincided with the attenuation of herbivore-induced CWI inhibition and growth suppression characteristic of wild-type plants. Together our findings suggest that NaCWII may act as a regulatory switch located downstream of JA accumulation which fine-tunes the plant's balance between growth and defense metabolism under herbivore attack. Although carbohydrates are not typically viewed as key factors in plant growth and defense, our study shows that interfering with their catabolism strongly influences plant responses to herbivory. PMID:26017581

  19. Generation of plasmin during acute attacks of hereditary angioedema.

    Science.gov (United States)

    Cugno, M; Hack, C E; de Boer, J P; Eerenberg, A J; Agostoni, A; Cicardi, M

    1993-01-01

    Hereditary angioedema is caused by a genetic deficiency of C1-inhibitor, a serine protease inhibitor that regulates activation of complement, contact, and fibrinolytic systems. Symptoms (bouts of subcutaneous and mucous swelling) depend on the release of a vasoactive mediator, probably through activation of these three systems. We studied the interrelationship among complement, contact, and fibrinolytic activation in 23 patients with hereditary angiodema, 18 during remission and five during an attack, by measuring plasma levels of C1-C1 inhibitor, factor XIIa-C1 inhibitor, kallikrein-C1 inhibitor, and plasmin-alpha 2-antiplasmin complexes, tissue plasminogen activator, and urokinase plasminogen activator. In addition, cleavage of high-molecular weight kininogen was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and quantified by densitometry. During remission, plasma levels of C1-C1 inhibitor complexes were elevated (p = 0.0002), whereas the other parameters were within the normal range. During acute attacks, not only plasma levels of C1-C1 inhibitor complexes but also those of plasmin-alpha 2-antiplasmin complexes (P = 0.0009) and cleaved high-molecular weight kininogen were elevated. A positive correlation between plasmin-alpha 2-antiplasmin complexes and cleaved high-molecular weight kininogen was observed (r = 0.75, p attacks is associated with the activation of the fibrinolytic system.

  20. PARP inhibitors in cancer therapy: two modes of attack on the cancer cell widening the clinical applications.

    Science.gov (United States)

    Drew, Yvette; Plummer, Ruth

    2009-12-01

    The abundant nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1) represents an important novel target in cancer therapy. PARP-1 is essential to the repair of single strand DNA breaks via the base excision repair pathway. Inhibitors of PARP-1 have been shown to enhance the cytotoxic effects of ionising radiation and DNA damaging chemotherapy agents such as the methylating agents and topoisomerase-I inhibitors. There are currently at least eight PARP inhibitors in clinical trial development. In vitro data, in vivo preclinical data and most recently early clinical trial data suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer associated (BRCA)1 and BRCA2 genes. This theory of selectively exploiting cells defective in one DNA repair pathway by inhibiting another is a major breakthrough in the treatment of cancer. The current clinical data are discussed within this review with reference to the preclinical models which predicted activity and also future directions and the possible dangers/pitfalls of this clinical strategy are explored.

  1. Predator attack rate evolution in space: the role of ecology mediated by complex emergent spatial structure and self-shading.

    Science.gov (United States)

    Messinger, Susanna M; Ostling, Annette

    2013-11-01

    Predation interactions are an important element of ecological communities. Population spatial structure has been shown to influence predator evolution, resulting in the evolution of a reduced predator attack rate; however, the evolutionary role of traits governing predator and prey ecology is unknown. The evolutionary effect of spatial structure on a predator's attack rate has primarily been explored assuming a fixed metapopulation spatial structure, and understood in terms of group selection. But endogenously generated, emergent spatial structure is common in nature. Furthermore, the evolutionary influence of ecological traits may be mediated through the spatial self-structuring process. Drawing from theory on pathogens, the evolutionary effect of emergent spatial structure can be understood in terms of self-shading, where a voracious predator limits its long-term invasion potential by reducing local prey availability. Here we formalize the effects of self-shading for predators using spatial moment equations. Then, through simulations, we show that in a spatial context self-shading leads to relationships between predator-prey ecology and the predator's attack rate that are not expected in a non-spatial context. Some relationships are analogous to relationships already shown for host-pathogen interactions, but others represent new trait dimensions. Finally, since understanding the effects of ecology using existing self-shading theory requires simplifications of the emergent spatial structure that do not apply well here, we also develop metrics describing the complex spatial structure of the predator and prey populations to help us explain the evolutionary effect of predator and prey ecology in the context of self-shading. The identification of these metrics may provide a step towards expansion of the predictive domain of self-shading theory to more complex spatial dynamics.

  2. Complex structure of a bacterial class 2 histone deacetylase homologue with a trifluoromethylketone inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Tine Kragh [Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik and GZMB, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Hildmann, Christian; Riester, Daniel; Wegener, Dennis; Schwienhorst, Andreas [Abteilung für Molekulare Genetik und Präparative Molekularbiologie, Institut für Mikrobiologie und Genetik, Grisebachstrasse 8, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@gwdg.de [Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik and GZMB, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

    2007-04-01

    The crystal structure of HDAH FB188 in complex with a trifluoromethylketone at 2.2 Å resolution is reported and compared to a previously determined inhibitor complex. Histone deacetylases (HDACs) have emerged as attractive targets in anticancer drug development. To date, a number of HDAC inhibitors have been developed and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA). Not surprisingly, structural information that can greatly enhance the design of novel HDAC inhibitors is so far only available for hydroxamic acids in complex with HDAC or HDAC-like enzymes. Here, the first structure of an enzyme complex with a nonhydroxamate HDAC inhibitor is presented. The structure of the trifluoromethyl ketone inhibitor 9,9,9-trifluoro-8-oxo-N-phenylnonanamide in complex with bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) has been determined. HDAH reveals high sequential and functional homology to human class 2 HDACs and a high structural homology to human class 1 HDACs. Comparison with the structure of HDAH in complex with SAHA reveals that the two inhibitors superimpose well. However, significant differences in binding to the active site of HDAH were observed. In the presented structure the O atom of the trifluoromethyl ketone moiety is within binding distance of the Zn atom of the enzyme and the F atoms participate in interactions with the enzyme, thereby involving more amino acids in enzyme–inhibitor binding.

  3. Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron

    International Nuclear Information System (INIS)

    The crystal structure of a novel MACPF protein, which may play a role in the adaptation of commensal bacteria to host environments in the human gut, was determined and analyzed. Membrane-attack complex/perforin (MACPF) proteins are transmembrane pore-forming proteins that are important in both human immunity and the virulence of pathogens. Bacterial MACPFs are found in diverse bacterial species, including most human gut-associated Bacteroides species. The crystal structure of a bacterial MACPF-domain-containing protein BT-3439 (Bth-MACPF) from B. thetaiotaomicron, a predominant member of the mammalian intestinal microbiota, has been determined. Bth-MACPF contains a membrane-attack complex/perforin (MACPF) domain and two novel C-terminal domains that resemble ribonuclease H and interleukin 8, respectively. The entire protein adopts a flat crescent shape, characteristic of other MACPF proteins, that may be important for oligomerization. This Bth-MACPF structure provides new features and insights not observed in two previous MACPF structures. Genomic context analysis infers that Bth-MACPF may be involved in a novel protein-transport or nutrient-uptake system, suggesting an important role for these MACPF proteins, which were likely to have been inherited from eukaryotes via horizontal gene transfer, in the adaptation of commensal bacteria to the host environment

  4. rhC1INH: a new drug for the treatment of attacks in hereditary angioedema caused by C1-inhibitor deficiency.

    Science.gov (United States)

    Varga, Lilian; Farkas, Henriette

    2011-03-01

    Recombinant human C1 esterase inhibitor (rhC1INH) (Ruconest(®), Pharming) is a new drug developed for the relief of symptoms occurring in patients with angioedema due to C1-inhibitor deficiency. Pertinent results have already been published elsewhere; this article summarizes the progress made since then. Similar to the purified C1-inhibitor derived from human plasma, the therapeutic efficacy of rhC1INH results from its ability to block the actions of enzymes belonging to the overactivated bradykinin-forming pathway, at multiple locations. During clinical trials into the management of acute edema, a total of 190 subjects received recombinant C1-inhibitor by intravenous infusion on 714 occasions altogether. Dose-ranging efficacy studies established 50 U/kg as the recommended dose, and demonstrated the effectiveness of this agent in all localizations of hereditary angioedema attacks. Studies into the safety of rhC1INH based on 300 administrations to healthy subjects or hereditary angioedema patients followed-up for 90 days have not detected the formation of autoantibodies against rhC1INH or IgE antibodies directed against rabbit proteins, even after repeated administration on multiple occasions. These findings met favorable appraisal by the EMA, which granted European marketing authorization for rhC1INH. Pharming is expected to file a biological licence with the US FDA by the end of 2010 to obtain marketing approval in the USA. The launch of rhC1INH onto the pharmaceutical market may represent an important progress in the management of hereditary angioedema patients. PMID:21426252

  5. rhC1INH: a new drug for the treatment of attacks in hereditary angioedema caused by C1-inhibitor deficiency.

    Science.gov (United States)

    Varga, Lilian; Farkas, Henriette

    2011-03-01

    Recombinant human C1 esterase inhibitor (rhC1INH) (Ruconest(®), Pharming) is a new drug developed for the relief of symptoms occurring in patients with angioedema due to C1-inhibitor deficiency. Pertinent results have already been published elsewhere; this article summarizes the progress made since then. Similar to the purified C1-inhibitor derived from human plasma, the therapeutic efficacy of rhC1INH results from its ability to block the actions of enzymes belonging to the overactivated bradykinin-forming pathway, at multiple locations. During clinical trials into the management of acute edema, a total of 190 subjects received recombinant C1-inhibitor by intravenous infusion on 714 occasions altogether. Dose-ranging efficacy studies established 50 U/kg as the recommended dose, and demonstrated the effectiveness of this agent in all localizations of hereditary angioedema attacks. Studies into the safety of rhC1INH based on 300 administrations to healthy subjects or hereditary angioedema patients followed-up for 90 days have not detected the formation of autoantibodies against rhC1INH or IgE antibodies directed against rabbit proteins, even after repeated administration on multiple occasions. These findings met favorable appraisal by the EMA, which granted European marketing authorization for rhC1INH. Pharming is expected to file a biological licence with the US FDA by the end of 2010 to obtain marketing approval in the USA. The launch of rhC1INH onto the pharmaceutical market may represent an important progress in the management of hereditary angioedema patients.

  6. Detrended Fluctuation Analysis on Correlations of Complex Networks Under Attack and Repair Strategy

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    We analyze the correlation properties of the Erdos-Rényi random graph (RG) and the Barabási-Albert scale-free network (SF) under the attack and repair strategy with detrended fluctuation analysis (DFA). The maximum degree k representing the local property of the system, shows similar scaling behaviors for random graphs and scale-free networks. The fluctuations are quite random at short time scales but display strong anticorrelation at longer time scales under the same system size N and different repair probability pre. The average degree , revealing the statistical property of the system, exhibits completely different scaling behaviors for random graphs and scale-free networks. Random graphs display long-range power-law correlations. Scale-free networks are uncorrelated at short time scales; while anticorrelated at longer time scales and the anticorrelation becoming stronger with the increase of pre.

  7. Numerical simulation by TVD schemes of complex shock reflections from airfoils at high angle of attack. [Total Variation Diminishing

    Science.gov (United States)

    Moon, Young J.; Yee, H. C.

    1987-01-01

    The shock-capturing capability of total variation diminishing (TVD) schemes is demonstrated for a more realistic complex shock-diffraction problem for which the experimental data are available. Second-order explicit upwind and symmetric TVD schemes are used to solve the time-dependent Euler equations of gas dynamics for the interaction of a blast wave with an airfoil at high angle-of-attack. The test cases considered are a time-dependent moving curved-shock wave and a contant moving planar-shock wave impinging at an angle-of-attack 30 deg on a NACA 0018 airfoil. Good agreement is obtained between isopycnic contours computed by the TVD schemes and those from experimental interferograms. No drastic difference in flow-field structure is found between the curved- and planar-shock wave cases, except for a difference in density level near the lower surface of the airfoil. Computation for cases with higher shock Mach numbers is also possible. Numerical experiments show that the symmetric TVD scheme is less sensitive to the boundary conditions treatment than the upwind scheme.

  8. Efficient reconfigurable hardware architecture for accurately computing success probability and data complexity of linear attacks

    DEFF Research Database (Denmark)

    Bogdanov, Andrey; Kavun, Elif Bilge; Tischhauser, Elmar;

    2012-01-01

    An accurate estimation of the success probability and data complexity of linear cryptanalysis is a fundamental question in symmetric cryptography. In this paper, we propose an efficient reconfigurable hardware architecture to compute the success probability and data complexity of Matsui's Algorithm...... in a vast range of parameters. The new hardware architecture allows us to verify the existing theoretical models for the complexity estimation in linear cryptanalysis. The designed hardware architecture is realized on two Xilinx Virtex-6 XC6VLX240T FPGAs for smaller block lengths, and on RIVYERA platform...

  9. Panic Attack or Heart Attack?

    Science.gov (United States)

    Panic Attack or Heart Attack? Diagnosing heart disease in women A Healthy Hearts Guide ® Heart disease in women is often mistaken for panic attack with shortness of breath, anxiety, palpitations and indigestion. ...

  10. CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Marquart, H V; Prodinger, W M;

    2001-01-01

    Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... convertase and consequent formation of membrane attack complexes (MAC). Deposition of C3 fragments and MAC was assessed on human peripheral B lymphocytes in the presence of 30% autologous serum containing 4.4 mM MgCl2/20 mM EGTA, which abrogates the classical pathway of complement without affecting...... the alternative pathway. Blockade of the CR2 ligand-binding site with the monoclonal antibody FE8 resulted in 56 +/- 13% and 71 +/- 9% inhibition of the C3-fragment and MAC deposition, respectively, whereas the monoclonal antibody HB135, directed against an irrelevant CR2 epitope, had no effect. Blockade...

  11. Crystal structure of a complex of human chymase with its benzimidazole derived inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yoshiyuki; Kakuda, Shinji; Koizumi, Masahiro; Mizuno, Tsuyoshi; Muroga, Yumiko; Kawamura, Takashi; Takimoto-Kamimura, Midori, E-mail: m.kamimura@teijin.co.jp [Teijin Institute for Bio-medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512 (Japan)

    2013-11-01

    The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The present study shows that the benzimidazole ring of the inhibitor takes the stable stacking interaction with the protonated His57 in the catalytic domain of human chymase. The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The X-ray crystallographic study shows that the benzimidazole inhibitor forms a non-covalent interaction with the catalytic domain of human chymase. The hydrophobic fragment of the inhibitor occupies the S1 pocket. The carboxylic acid group of the inhibitor forms hydrogen bonds with the imidazole N(∊) atom of His57 and/or the O(γ) atom of Ser195 which are members of the catalytic triad. This imidazole ring of His57 induces π–π stacking to the benzene ring of the benzimidazole scaffold as P2 moiety. Fragment molecular orbital calculation of the atomic coordinates by X-ray crystallography shows that this imidazole ring of His57 could be protonated with the carboxyl group of Asp102 or hydroxyl group of Ser195 and the stacking interaction is stabilized. A new drug design strategy is proposed where the stacking to the protonated imidazole of the drug target protein with the benzimidazole scaffold inhibitor causes unpredicted potent inhibitory activity for some enzymes.

  12. [Proteinase-proteinase inhibitor complex in rats under oxidative stress caused by administration of cobalt chloride].

    Science.gov (United States)

    Kaliman, P A; Samokhin, A A; Samokhina, L M

    2000-01-01

    Mechanisms of proteinase-inhibitor proteinase system response was estimated following of cobalt chloride injection. The increase proteinase activity, which led to significant decrease of alpha-2-macroglobulin (alpha-2-MG) level was established that indicated to the removal of the proteinase in complex with alpha-2-MG from the organism. Increase of alpha-1-proteinase inhibitor (alpha-1-PI) trypsin-inhibitory activity in the kidneys testify about removal of oxidative alpha-1-PI. PMID:10979565

  13. Using AI and Semantic Web Technologies to attack Process Complexity in Open Systems

    Science.gov (United States)

    Thompson, Simon; Giles, Nick; Li, Yang; Gharib, Hamid; Nguyen, Thuc Duong

    Recently many vendors and groups have advocated using BPEL and WS-BPEL as a workflow language to encapsulate business logic. While encapsulating workflow and process logic in one place is a sensible architectural decision the implementation of complex workflows suffers from the same problems that made managing and maintaining hierarchical procedural programs difficult. BPEL lacks constructs for logical modularity such as the requirements construct from the STL [12] or the ability to adapt constructs like pure abstract classes for the same purpose. We describe a system that uses semantic web and agent concepts to implement an abstraction layer for BPEL based on the notion of Goals and service typing. AI planning was used to enable process engineers to create and validate systems that used services and goals as first class concepts and compiled processes at run time for execution.

  14. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus.

    Science.gov (United States)

    Girish, Vallerinteavide Mavelli; Kini, R Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki' and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  15. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus

    Science.gov (United States)

    Girish, Vallerinteavide Mavelli; Kini, R. Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki’ and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  16. Inhibitors

    Science.gov (United States)

    ... wrong place in the body. Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from ... body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor ...

  17. Crystal structure of two new bifunctional nonsubstrate type thrombin inhibitors complexed with human alpha-thrombin.

    Science.gov (United States)

    Féthière, J.; Tsuda, Y.; Coulombe, R.; Konishi, Y.; Cygler, M.

    1996-01-01

    The crystal structures of two new thrombin inhibitors, P498 and P500, complexed with human alpha-thrombin have been determined at 2.0 A resolution and refined to crystallographic R-factors of 0.170 and 0.169, respectively. These compounds, with picomolar binding constants, belong to a family of potent bifunctional inhibitors that bind thrombin at two remote sites: the active site and the fibrinogen recognition exosite (FRE). The inhibitors incorporate a nonsubstrate type active site binding fragment: Dansyl-Arg-(D)Pipecolic acid (Dns-Arg-(D)Pip), reminiscent of the active-site directed inhibitors MD-805 and MQPA, rendering them resistant to thrombin-induced hydrolysis. The FRE binding fragment of these inhibitors corresponds to the hirudin55-65 sequence. They differ in the chemical nature of the nonpeptidyl linker bridging these two functional activities. In both cases, the active site binding fragment is well defined in the electron density. The DnsH1, ArgH2, and (D)PipH3 groups occupy the S3, S1, and S2 subsites of thrombin, respectively, in a way similar to that observed in the thrombin-MQPA complexes. Binding in the active site of thrombin is characterized by numerous van der Waals contacts and ring-ring system interactions. Unlike in the substrate-like inhibitors, ArgH2 enters the S1 specificity pocket from the P2 position and adopts a bent conformation to make an hydrogen bond to the carboxylate of Asp189. In this noncanonical position, its carbonyl points away from the oxyanion hole, which is now occupied by well-ordered solvent molecules. The linkers fit in the groove extending from the active site to the FRE. The C-terminal fragments of both inhibitors bind in the same way as analogous FRE binding elements in previously described complexes. PMID:8762149

  18. Metabolic responses in Candida tropicalis to complex inhibitors during xylitol bioconversion.

    Science.gov (United States)

    Wang, Shizeng; Li, Hao; Fan, Xiaoguang; Zhang, Jingkun; Tang, Pingwah; Yuan, Qipeng

    2015-09-01

    During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1,3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1,3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource. PMID:26127015

  19. Aspects of preanalytical variation of lactoferrin and elastase/alpha 1-protease inhibitor complexes

    DEFF Research Database (Denmark)

    Antonsen, S; Qvist, N; Wanscher, M

    1993-01-01

    A number of interesting applications of plasma elastase/alpha 1-protease inhibitor complexes (ELA-PI) and lactoferrin (LAC) have recently been suggested. However, the clinical utility of these components often seems to be low. This might be improved by minimizing the preanalytical variation...

  20. Mitochondrial Complex I Inhibitors and Forced Oxidative Phosphorylation Synergize in Inducing Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Roberta Palorini

    2013-01-01

    Full Text Available Cancer cells generally rely mostly on glycolysis rather than oxidative phosphorylation (OXPHOS for ATP production. In fact, they are particularly sensitive to glycolysis inhibition and glucose depletion. On the other hand mitochondrial dysfunctions, involved in the onset of the Warburg effect, are sometimes also associated with the resistance to apoptosis that characterizes cancer cells. Therefore, combined treatments targeting both glycolysis and mitochondria function, exploiting peculiar tumor features, might be lethal for cancer cells. In this study, we show that glucose deprivation and mitochondrial Complex I inhibitors synergize in inducing cancer cell death. In particular, our results reveal that low doses of Complex I inhibitors, ineffective on immortalized cells and in high glucose growth, become specifically cytotoxic on cancer cells deprived of glucose. Importantly, the cytotoxic effect of the inhibitors on cancer cells is strongly enhanced by forskolin, a PKA pathway activator, that we have previously shown to stimulate OXPHOS. Taken together, we demonstrate that induction in cancer cells of a switch from a glycolytic to a more respirative metabolism, obtained by glucose depletion or mitochondrial activity stimulation, strongly increases their sensitivity to low doses of mitochondrial Complex I inhibitors. Our findings might be a valuable approach to eradicate cancer cells.

  1. Systemic effects of treatment with mTOR inhibitors in tuberous sclerosis complex: a comprehensive review.

    Science.gov (United States)

    Sadowski, K; Kotulska, K; Schwartz, R A; Jóźwiak, S

    2016-04-01

    Tuberous sclerosis complex (TSC) is a genetic multisystem disorder associated with constitutive overactivation of the mammalian target of rapamycin (mTOR) pathway and characterized by development of benign tumours in various organs. mTOR inhibitors have proven to be effective in the targeted therapy of certain TSC-associated pathologies such as subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas (AMLs). Accumulating experimental and clinical data suggest that mTOR inhibitors might have a systemic, disease-modifying influence on affected individuals. This systematic review provides an analysis of available clinical data concerning systemic effect of mTOR inhibitors and the influence of mTOR inhibition on different manifestations of TSC in individual patients.

  2. Attack surfaces

    DEFF Research Database (Denmark)

    Gruschka, Nils; Jensen, Meiko

    2010-01-01

    The new paradigm of cloud computing poses severe security risks to its adopters. In order to cope with these risks, appropriate taxonomies and classification criteria for attacks on cloud computing are required. In this work-in-progress paper we present one such taxonomy based on the notion...... of attack surfaces of the cloud computing scenario participants. © 2010 IEEE....

  3. Heart Attack

    Science.gov (United States)

    ... a million people in the U.S. have a heart attack. About half of them die. Many people have permanent heart damage or die because they don't get ... It's important to know the symptoms of a heart attack and call 9-1-1 if someone ...

  4. Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor.

    Directory of Open Access Journals (Sweden)

    Alex N Bullock

    Full Text Available BACKGROUND: The serine/threonine kinase PIM2 is highly expressed in human leukemia and lymphomas and has been shown to positively regulate survival and proliferation of tumor cells. Its diverse ATP site makes PIM2 a promising target for the development of anticancer agents. To date our knowledge of catalytic domain structures of the PIM kinase family is limited to PIM1 which has been extensively studied and which shares about 50% sequence identity with PIM2. PRINCIPAL FINDINGS: Here we determined the crystal structure of PIM2 in complex with an organoruthenium complex (inhibition in sub-nanomolar level. Due to its extraordinary shape complementarity this stable organometallic compound is a highly potent inhibitor of PIM kinases. SIGNIFICANCE: The structure of PIM2 revealed several differences to PIM1 which may be explored further to generate isoform selective inhibitors. It has also demonstrated how an organometallic inhibitor can be adapted to the binding site of protein kinases to generate highly potent inhibitors. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

  5. A preliminary neutron crystallography on the trypsin-bovine pancreatic trypsin inhibitor complex

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, K; Yamada, T; Kurihara, K; Tamada, T; Kuroki, R; Tanaka, I; Takahashi, H; Niimura, N, E-mail: niimura@mx.ibaraki.ac.jp

    2010-11-01

    Trypsin is one of serine proteases. BPTI (Bovine Pancreatic Trypsin Inhibitor) is a protein inhibitor, which binds trypsin tightly and inhibits cleavage of peptide bonds. X-ray structure determination of trypsin-BPTI complex could make clear the overview of the active site. However, information of hydrogen atoms related to catalytic mechanism has not been satisfied. In this study, the trypsin-BPTI complex structure has been determined by neutron diffraction data at 2.0 A resolution. Deuterium atoms of catalytic triad, hydration structures in the binding pocket of trypsin and hydrogen bonds were observed. We would like to discuss details of hydrogen bonds in the interface between trypsin and BPTI and the adjacent water molecules including hydrogen atoms involved in the enzymatic reaction.

  6. Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor-1

    Directory of Open Access Journals (Sweden)

    Huang Mingdong

    2011-06-01

    Full Text Available Abstract Background Matriptase is a type II transmembrane serine protease that is found on the surfaces of epithelial cells and certain cancer cells. Matriptase has been implicated in the degradation of certain extracellular matrix components as well as the activation of various cellular proteins and proteases, including hepatocyte growth factor and urokinase. Sunflower trypsin inhibitor-1 (SFTI-1, a cyclic peptide inhibitor originally isolated from sunflower seeds, exhibits potent inhibitory activity toward matriptase. Results We have engineered and produced recombinant proteins of the matriptase protease domain, and have determined the crystal structures of the protease:SFTI-1 complex at 2.0 Å as well as the protease:benzamidine complex at 1.2 Å. These structures elaborate the structural basis of substrate selectivity of matriptase, and show that the matriptase S1 substrate specificity pocket is larger enough to allow movement of benzamidine inside the S1 pocket. Our study also reveals that SFTI-1 binds to matriptase in a way similar to its binding to trypsin despite the significantly different isoelectric points of the two proteins (5.6 vs. 8.2. Conclusions This work helps to define the structural basis of substrate specificity of matriptase and the interactions between the inhibitor and protease. The complex structure also provides a structural template for designing new SFTI-1 derivatives with better potency and selectivity against matriptase and other proteases.

  7. Panic Attack

    OpenAIRE

    Scantamburlo, Gabrielle; Ansseau, Marc

    2004-01-01

    Panic attacks can occur unexpectedly and in almost any situation. The present article discusses the main features of anxiety states, the approach, the management and the practice guidelines for the treatment of panic disorder. Peer reviewed

  8. [Panic attack].

    Science.gov (United States)

    Scantamburlo, G; Ansseau, M

    2004-05-01

    Panic attacks can occur unexpectedly and in almost any situation. The present article discusses the main features of anxiety states, the approach, the management and the practice guidelines for the treatment of panic disorder. PMID:15264579

  9. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2

    DEFF Research Database (Denmark)

    Mølgaard, Anne; Arnau, Jose; Lauritzen, C.;

    2007-01-01

    . In the present paper, we provide the first crystal structure of an hDPPI-inhibitor complex. The inhibitor Gly-Phe-CHN2 (Gly-Phe-diazomethane) was co-crystallized with hDPPI and the structure was determined at 2.0 angstrom (1 angstrom = 0.1 nm) resolution. The structure of the native enzyme was also determined...... to 2.05 angstrom resolution to resolve apparent discrepancies between the complex structure and the previously published structure of the native enzyme. The new structure of the native enzyme is, within the experimental error, identical with the structure of the enzyme-inhibitor complex presented here....... The inhibitor interacts with three subunits of hDPPI, and is covalently bound to Cys(234) at the active site. The interaction between the totally conserved Asp(1) of hDPPI and the ammonium group of the inhibitor forms an essential interaction that mimics enzyme-substrate interactions. The structure...

  10. Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

    Science.gov (United States)

    Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

    2016-03-28

    The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches. PMID:26848511

  11. Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

    Science.gov (United States)

    Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

    2016-03-28

    The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches.

  12. Structure-based lead discovery for protein kinase C zeta inhibitor design by exploiting kinase-inhibitor complex crystal structure data and potential therapeutics for preterm labour.

    Science.gov (United States)

    Shao, Qing-Chun; Zhang, Cui-Juan; Li, Jie

    2014-10-14

    The protein kinase C (PKC) is a family of serine/threonine kinases with a broad range of cellular targets. Members of the PKC family participate at the diverse biological events involved in cellular proliferation, differentiation and survival. The PKC isoform zeta (PKCζ) is an atypical member that has recently been found to play an essential role in promoting human uterine contractility and thus been raised as a new target for treating preterm labour and other tocolytic diseases. In this study, an integrative protocol was described to graft hundreds of inhibitor ligands from their complex crystal structures with cognate kinases into the active pocket of PKCζ and, based on the modeled structures, to evaluate the binding strength of these inhibitors to the non-cognate PKCζ receptor by using a consensus scoring strategy. A total of 32 inhibitors with top score were compiled, and eight out of them were tested for inhibitory potency against PKCζ. Consequently, five compounds, i.e. CDK6 inhibitor fisetin, PIM1 inhibitor myricetin, CDK9 inhibitor flavopiridol and PknB inhibitor mitoxantrone as well as the promiscuous kinase inhibitor staurosporine showed high or moderate inhibitory activity on PKCζ, with IC50 values of 58 ± 9, 1.7 ± 0.4, 108 ± 17, 280 ± 47 and 0.019 ± 0.004 μM, respectively, while other three compounds, including two marketed drugs dasatinib and sunitinib as well as the Rho inhibitor fasudil, have not been detected to possess observable activity. Next, based on the modeled structure data we modified three flavonoid kinase inhibitors, i.e. fisetin, myricetin and flavopiridol, to generate a number of more potential molecular entities, two of which were found to have a moderately improved activity as compared to their parent compounds.

  13. Sertraline-induced panic attack.

    Science.gov (United States)

    González-Berríos, Nereida

    2009-01-01

    Selective Serotonin Reuptake Inhibitors are the treatment of choice for depression and anxiety disorders due to its tolerability, safety and side effects profile. However, with the current and frequent use of these medications in patients with these disorders, new side effects have been reported. This case report describes the development of panic attacks in a 24-year-old-female patient with depressive and anxiety symptoms, and no previous predisposing history for panic attacks. PMID:19954091

  14. Improving Attack Graph Visualization through Data Reduction and Attack Grouping

    Energy Technology Data Exchange (ETDEWEB)

    John Homer; Ashok Varikuti; Xinming Ou; Miles A. McQueen

    2008-09-01

    Various tools exist to analyze enterprise network systems and to produce attack graphs detailing how attackers might penetrate into the system. These attack graphs, however, are often complex and difficult to comprehend fully, and a human user may find it problematic to reach appropriate configuration decisions. This paper presents methodologies that can 1) automatically identify portions of an attack graph that do not help a user to understand the core security problems and so can be trimmed, and 2) automatically group similar attack steps as virtual nodes in a model of the network topology, to immediately increase the understandability of the data. We believe both methods are important steps toward improving visualization of attack graphs to make them more useful in configuration management for large enterprise networks. We implemented our methods using one of the existing attack-graph toolkits. Initial experimentation shows that the proposed approaches can 1) significantly reduce the complexity of attack graphs by trimming a large portion of the graph that is not needed for a user to understand the security problem, and 2) significantly increase the accessibility and understandability of the data presented in the attack graph by clearly showing, within a generated visualization of the network topology, the number and type of potential attacks to which each host is exposed.

  15. Structural and biochemical characterization of the inhibitor complexes of xenotropic murine leukemia virus-related virus protease

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi; Gustchina, Alla; Matúz, Krisztina; Tözsér, Jozsef; Namwong, Sirilak; Goldfarb, Nathan E.; Dunn, Ben M.; Wlodawer, Alexander (Debrecen); (NCI); (Florida); (Suan Sunandha)

    2012-10-23

    Interactions between the protease (PR) encoded by the xenotropic murine leukemia virus-related virus and a number of potential inhibitors have been investigated by biochemical and structural techniques. It was observed that several inhibitors used clinically against HIV PR exhibit nanomolar or even subnanomolar values of K{sub i}, depending on the exact experimental conditions. Both TL-3, a universal inhibitor of retroviral PRs, and some inhibitors originally shown to inhibit plasmepsins were also quite potent, whereas inhibition by pepstatin A was considerably weaker. Crystal structures of the complexes of xenotropic murine leukemia virus-related virus PR with TL-3, amprenavir and pepstatin A were solved at high resolution and compared with the structures of complexes of these inhibitors with other retropepsins. Whereas TL-3 and amprenavir bound in a predictable manner, spanning the substrate-binding site of the enzyme, two molecules of pepstatin A bound simultaneously in an unprecedented manner, leaving the catalytic water molecule in place.

  16. Soluble form of membrane attack complex independently predicts mortality and cardiovascular events in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Lindberg, Søren; Pedersen, Sune H; Mogelvang, Rasmus;

    2012-01-01

    The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes...... to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC in patients with ST-segment elevation myocardial...

  17. The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes

    DEFF Research Database (Denmark)

    Leslie, Robert Graham Quinton; Nielsen, Claus Henrik

    2004-01-01

    The contributions of the classical (CP) and alternative (AP) pathways of complement activation to the spontaneous deposition of C3 fragments and the formation of membrane attack complexes (MAC) on human B lymphocytes, were assessed by incubating peripheral blood mononuclear cells with autologous......, however, in the nature of the fragments deposited as a result of CP and AP activation: C3b fragments deposited via the CP were extensively ( approximately 90%) converted to the terminal degradation product, C3dg, whereas about 50% of those deposited by the AP persisted as C3b/iC3b fragments. The extent of...

  18. Shark attack.

    Science.gov (United States)

    Guidera, K J; Ogden, J A; Highhouse, K; Pugh, L; Beatty, E

    1991-01-01

    Shark attacks are rare but devastating. This case had major injuries that included an open femoral fracture, massive hemorrhage, sciatic nerve laceration, and significant skin and muscle damage. The patient required 15 operative procedures, extensive physical therapy, and orthotic assistance. A review of the literature pertaining to shark bites is included.

  19. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Science.gov (United States)

    Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G; Schimel, Jeff; Webber, David

    2014-01-01

    Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  20. Hepatitis C Virus (HCV) NS5B Nonnucleoside Inhibitors Specifically Block Single-Stranded Viral RNA Synthesis Catalyzed by HCV Replication Complexes In Vitro▿

    OpenAIRE

    Yang, Wengang; Sun, Yongnian; Phadke, Avinash; Deshpande, Milind; Huang, Mingjun

    2006-01-01

    Replication complexes of hepatitis C virus synthesized two major species of viral RNA in vitro, double stranded and single stranded. NS5B nonnucleoside inhibitors inhibited dose dependently the synthesis of single-stranded RNA but not double-stranded RNA. Moreover, replication complexes carrying a mutation resistant to a nonnucleoside inhibitor lost their susceptibilities to the inhibitor.

  1. Characterization of Two Classes of Small Molecule Inhibitors of Arp2/3 Complex

    Energy Technology Data Exchange (ETDEWEB)

    Nolen, B.; Tomasevic, N; Russell, A; Pierce, D; Jia, Z; McCormick, C; Hartman, J; Sakowicz, R; Pollard, T

    2009-01-01

    Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.

  2. Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor.

    Science.gov (United States)

    Li, De Feng; Zhang, Jia Yue; Hou, Yan Jie; Liu, Lei; Hu, Yonglin; Liu, Shuang Jiang; Wang, Da Cheng; Liu, Wei

    2013-01-01

    Dioxygen activation by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Here, crystal structures of 2-aminophenol 1,6-dioxygenase, an enzyme that represents a minor group of extradiol dioxygenases and that catalyses the ring opening of 2-aminophenol, in complex with the lactone intermediate (4Z,6Z)-3-iminooxepin-2(3H)-one and the product 2-aminomuconic 6-semialdehyde and in complex with the suicide inhibitor 4-nitrocatechol are reported. The Fe-ligand binding schemes observed in these structures revealed some common geometrical characteristics that are shared by the published structures of extradiol dioxygenases, suggesting that enzymes that catalyse the oxidation of noncatecholic compounds are very likely to utilize a similar strategy for dioxygen activation and the fission of aromatic rings as the canonical mechanism. The Fe-ligation arrangement, however, is strikingly enantiomeric to that of all other 2-His-1-carboxylate enzymes apart from protocatechuate 4,5-dioxygenase. This structural variance leads to the generation of an uncommon O(-)-Fe(2+)-O(-) species prior to O(2) binding, which probably forms the structural basis on which APD distinguishes its specific substrate and inhibitor, which share an analogous molecular structure.

  3. Performance of attack strategies on modular networks

    CERN Document Server

    da Cunha, Bruno Requião

    2016-01-01

    Vulnerabilities of complex networks have became a trend topic in complex systems recently due to its real world applications. Most real networks tend to be very fragile to high betweenness adaptive attacks. However, recent contributions have shown the importance of interconnected nodes in the integrity of networks and module-based attacks have appeared promising when compared to traditional malicious non-adaptive attacks. In the present work we deeply explore the trade-off associated with attack procedures, introducing a generalized robustness measure and presenting an attack performance index that takes into account both robustness of the network against the attack and the run-time needed to obtained the list of targeted nodes for the attack. Besides, we introduce the concept of deactivation point aimed to mark the point at which the network stops to function properly. We then show empirically that non-adaptive module-based attacks perform better than high degree and betweenness adaptive attacks in networks ...

  4. Mars attacks.

    Science.gov (United States)

    Cohain, Judy Slome

    2008-01-01

    "Mars Attacks" is a new term coined to describe unjustified violation of women by care providers at the time of birth, as well as the purposeful abandonment of the peer review system by major obstetric journals and the abandonment of the use of research evidence by ACOG in their latest protocols, in order to justify continued use of this form of violence against women. PMID:19244777

  5. Heart Attack Risk Assessment

    Science.gov (United States)

    ... Pressure Tools & Resources Stroke More Heart Attack Risk Assessment Updated:May 31,2016 We're sorry, but ... Can You Recognize a Heart Attack? Quiz Risk Assessment Patient Information Sheets: Heart Attack Heart Attack Personal ...

  6. Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor.

    Science.gov (United States)

    Esler, Murray; Lambert, Elisabeth; Alvarenga, Marlies; Socratous, Florentia; Richards, Jeff; Barton, David; Pier, Ciaran; Brenchley, Celia; Dawood, Tye; Hastings, Jacqueline; Guo, Ling; Haikerwal, Deepak; Kaye, David; Jennings, Garry; Kalff, Victor; Kelly, Michael; Wiesner, Glen; Lambert, Gavin

    2007-08-01

    Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain

  7. Probing the structure-activity relationship of endogenous histone deacetylase complexes with immobilized peptide-inhibitors.

    Science.gov (United States)

    Sindlinger, Julia; Bierlmeier, Jan; Geiger, Lydia-Christina; Kramer, Katharina; Finkemeier, Iris; Schwarzer, Dirk

    2016-05-01

    Histone deacetylases (HDACs) are key regulators of numerous cellular proteins by removing acetylation marks from modified lysine residues. Peptide-based HDAC probes containing α-aminosuberic acid ω-hydroxamate have been established as useful tools for investigating substrate selectivity and composition of endogenous HDAC complexes in cellular lysates. Here we report a structure-activity study of potential HDAC-probes containing derivatives of the hydroxamate moieties. While most of these probes did not recruit significant amounts of endogenous HDACs from cellular lysates, peptides containing Nε-acetyl-Nε-hydroxy-L-lysine served as HDAC probe. The recruitment efficiency varied between HDACs and was generally lower than that of α-aminosuberic acid ω-hydroxamate probes, but showed a similar global interaction profile. These findings indicate that Nε-acetyl-Nε-hydroxy-L-lysine might be a useful tool for investigations on HDAC complexes and the development of HDAC inhibitors. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27071932

  8. Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor.

    Science.gov (United States)

    Lei, Jian; Hansen, Guido; Nitsche, Christoph; Klein, Christian D; Zhang, Linlin; Hilgenfeld, Rolf

    2016-07-29

    The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp(83) of NS2B; ion-pairing between Asp(83) and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing. PMID:27386922

  9. Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

    LENUS (Irish Health Repository)

    McCabe, Dominick J H

    2004-06-01

    Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and\\/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P <\\/= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P <\\/= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and\\/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

  10. Novel Inhibitors Complexed with Glutamate Dehydrogenase: ALLOSTERIC REGULATION BY CONTROL OF PROTEIN DYNAMICS

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ming; Smith, Christopher J.; Walker, Matthew T.; Smith, Thomas J.; (Danforth)

    2009-12-01

    Mammalian glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate using NAD(P){sup +} as coenzyme. Unlike its counterparts from other animal kingdoms, mammalian GDH is regulated by a host of ligands. The recently discovered hyperinsulinism/hyperammonemia disorder showed that the loss of allosteric inhibition of GDH by GTP causes excessive secretion of insulin. Subsequent studies demonstrated that wild-type and hyperinsulinemia/hyperammonemia forms of GDH are inhibited by the green tea polyphenols, epigallocatechin gallate and epicatechin gallate. This was followed by high throughput studies that identified more stable inhibitors, including hexachlorophene, GW5074, and bithionol. Shown here are the structures of GDH complexed with these three compounds. Hexachlorophene forms a ring around the internal cavity in GDH through aromatic stacking interactions between the drug and GDH as well as between the drug molecules themselves. In contrast, GW5074 and bithionol both bind as pairs of stacked compounds at hexameric 2-fold axes between the dimers of subunits. The internal core of GDH contracts when the catalytic cleft closes during enzymatic turnover. None of the drugs cause conformational changes in the contact residues, but all bind to key interfaces involved in this contraction process. Therefore, it seems likely that the drugs inhibit enzymatic turnover by inhibiting this transition. Indeed, this expansion/contraction process may play a major role in the inter-subunit communication and allosteric regulation observed in GDH.

  11. Heart Attack Recovery FAQs

    Science.gov (United States)

    ... Pressure High Blood Pressure Tools & Resources Stroke More Heart Attack Recovery FAQs Updated:Aug 24,2016 Most people ... recovery. View an animation of a heart attack . Heart Attack Recovery Questions and Answers What treatments will I ...

  12. Complexes of Imidazole with Poly(ethylene glycol) as a Corrosion Inhibitor for Carbon Steel in Sulphuric Acid

    Science.gov (United States)

    Salimi, Saeed; Nasr-Esfahani, Mojtaba; Umoren, Saviour A.; Saebnoori, Ehsan

    2015-12-01

    The inhibiting action of polyethylene glycol and imidazole (PEG/IMZ)) complexes prepared by a simple deprotonation procedure on carbon steel corrosion in 0.5 mol/L sulphuric acid was evaluated using the weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy techniques complemented by surface analysis using scanning electron microscopy. The inhibiting effect of the PEG/IMZ complexes on carbon steel corrosion was compared with the non-complex forms. Results obtained show that PEG/IMZ complex is a very effective corrosion inhibitor of carbon steel in the acid environment. The inhibition efficiency increased with the increase in the temperature and also with increasing percentage of imidazole in the complex. Corrosion inhibition occurs by virtue of adsorption of PEG/IMZ complexes on the steel surface which was found to follow the Temkin adsorption isotherm model. The PEG/IMZ complexes function as a mixed-type inhibitor. Results from all the methods employed are in a reasonably good agreement.

  13. Assembly and Regulation of the Membrane Attack Complex Based on Structures of C5b6 and sC5b9

    Directory of Open Access Journals (Sweden)

    Michael A. Hadders

    2012-03-01

    Full Text Available Activation of the complement system results in formation of membrane attack complexes (MACs, pores that disrupt lipid bilayers and lyse bacteria and other pathogens. Here, we present the crystal structure of the first assembly intermediate, C5b6, together with a cryo-electron microscopy reconstruction of a soluble, regulated form of the pore, sC5b9. Cleavage of C5 to C5b results in marked conformational changes, distinct from those observed in the homologous C3-to-C3b transition. C6 captures this conformation, which is preserved in the larger sC5b9 assembly. Together with antibody labeling, these structures reveal that complement components associate through sideways alignment of the central MAC-perforin (MACPF domains, resulting in a C5b6-C7-C8β-C8α-C9 arc. Soluble regulatory proteins below the arc indicate a potential dual mechanism in protection from pore formation. These results provide a structural framework for understanding MAC pore formation and regulation, processes important for fighting infections and preventing complement-mediated tissue damage.

  14. Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors.

    Science.gov (United States)

    Prato, Giulia; Mancardi, Maria Margherita; Baglietto, Maria Giuseppina; Janis, Sara; Vercellino, Nadia; Rossi, Andrea; Consales, Alessandro; Raso, Alessandro; Garrè, Maria Luisa

    2014-09-01

    Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy. PMID:24056156

  15. Crystal Structure of 12-Lipoxygenase Catalytic-Domain-Inhibitor Complex Identifies a Substrate-Binding Channel for Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Shu; Mueser, Timothy C.; Marnett, Lawrence J.; Funk, Jr., Max O. (Toledo); (Vanderbilt)

    2014-10-02

    Lipoxygenases are critical enzymes in the biosynthesis of families of bioactive lipids including compounds with important roles in the initiation and resolution of inflammation and in associated diseases such as diabetes, cardiovascular disease, and cancer. Crystals diffracting to high resolution (1.9 {angstrom}) were obtained for a complex between the catalytic domain of leukocyte 12-lipoxygenase and the isoform-specific inhibitor, 4-(2-oxapentadeca-4-yne)phenylpropanoic acid (OPP). In the three-dimensional structure of the complex, the inhibitor occupied a new U-shaped channel open at one end to the surface of the protein and extending past the redox-active iron site that is essential for catalysis. In models, the channel accommodated arachidonic acid, defining the binding site for the substrate of the catalyzed reaction. There was a void adjacent to the OPP binding site connecting to the surface of the enzyme and providing a plausible access channel for the other substrate, oxygen.

  16. Genetic attack on neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Naeh, Rivka; Kanter, Ido

    2006-03-01

    Different scaling properties for the complexity of bidirectional synchronization and unidirectional learning are essential for the security of neural cryptography. Incrementing the synaptic depth of the networks increases the synchronization time only polynomially, but the success of the geometric attack is reduced exponentially and it clearly fails in the limit of infinite synaptic depth. This method is improved by adding a genetic algorithm, which selects the fittest neural networks. The probability of a successful genetic attack is calculated for different model parameters using numerical simulations. The results show that scaling laws observed in the case of other attacks hold for the improved algorithm, too. The number of networks needed for an effective attack grows exponentially with increasing synaptic depth. In addition, finite-size effects caused by Hebbian and anti-Hebbian learning are analyzed. These learning rules converge to the random walk rule if the synaptic depth is small compared to the square root of the system size.

  17. Structure of Human G Protein-Coupled Receptor Kinase 2 in Complex with the Kinase Inhibitor Balanol

    Energy Technology Data Exchange (ETDEWEB)

    Tesmer, John J.G.; Tesmer, Valerie M.; Lodowski, David T.; Steinhagen, Henning; Huber, Jochen (Sanofi); (Michigan); (Texas)

    2010-07-19

    G protein-coupled receptor kinase 2 (GRK2) is a pharmaceutical target for the treatment of cardiovascular diseases such as congestive heart failure, myocardial infarction, and hypertension. To better understand how nanomolar inhibition and selectivity for GRK2 might be achieved, we have determined crystal structures of human GRK2 in complex with G{beta}{gamma} in the presence and absence of the AGC kinase inhibitor balanol. The selectivity of balanol among human GRKs is assessed.

  18. Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I.

    Science.gov (United States)

    Thomas, Simmy; Sharma, Natasha; Gonzalez, Reyna; Pao, Peng-Wen; Hofman, Florence M; Chen, Thomas C; Louie, Stan G; Pirrung, Michael C; Schönthal, Axel H

    2013-01-01

    Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD's strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed. PMID:23755268

  19. Repositioning of Verrucosidin, a purported inhibitor of chaperone protein GRP78, as an inhibitor of mitochondrial electron transport chain complex I.

    Directory of Open Access Journals (Sweden)

    Simmy Thomas

    Full Text Available Verrucosidin (VCD belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78 expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose, but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin. However, VCD's strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin might act in a similar GRP78-independent fashion will be discussed.

  20. A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    A Kolyada; C Lee; A De Biasio; N Beglova

    2011-12-31

    {beta}2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of {beta}2GPI generated by anti-{beta}2GPI antibodies is pathologically important, in contrast to monomeric {beta}2GPI which is abundant in plasma. We created a dimeric inhibitor, A1-A1, to selectively target {beta}2GPI in {beta}2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of {beta}2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of {beta}2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of {beta}2GPI present in human serum, {beta}2GPI purified from human plasma and the individual domain V of {beta}2GPI. We demonstrated that when {beta}2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of {beta}2GPI to cardiolipin, regardless of the source of {beta}2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of {beta}2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-{beta}2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric {beta}2GPI to cardiolipin. Our results suggest that the approach of using a dimeric inhibitor to block {beta}2GPI in the pathological multivalent {beta}2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.

  1. A novel dimeric inhibitor targeting Beta2GPI in Beta2GPI/antibody complexes implicated in antiphospholipid syndrome.

    Directory of Open Access Journals (Sweden)

    Alexey Kolyada

    Full Text Available BACKGROUND: β2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS, an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of β2GPI generated by anti-β2GPI antibodies is pathologically important, in contrast to monomeric β2GPI which is abundant in plasma. PRINCIPAL FINDINGS: We created a dimeric inhibitor, A1-A1, to selectively target β2GPI in β2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1 and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of β2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of β2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of β2GPI present in human serum, β2GPI purified from human plasma and the individual domain V of β2GPI. We demonstrated that when β2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of β2GPI to cardiolipin, regardless of the source of β2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of β2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-β2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric β2GPI to cardiolipin. CONCLUSIONS: Our results suggest that the approach of using a dimeric inhibitor to block β2GPI in the pathological multivalent β2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.

  2. The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma: Relation to prognosis

    DEFF Research Database (Denmark)

    Pappot, Helle; Pedersen, Anders N; Brünner, Nils;

    2006-01-01

    In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated....... The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found...... these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers....

  3. The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) in pulmonary adenocarcinoma

    DEFF Research Database (Denmark)

    Pappot, Helle; Pedersen, Anders N.; Brünner, Nils;

    2006-01-01

    In a lung cancer population comprising tumor tissue from 99 pulmonary adenocarcinoma patients, the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival was studied. The study included patient material previously investigated....... The amounts of uPA-PAI-1 complex measured in pulmonary adenocarcinoma tissue were within the same range as previously reported in breast cancer tissue (0.11-5.74 ng/mg protein). uPA and PAI-1 levels were weakly correlated to the uPA-PAI-1 complex, r = 0.52 and r = 0.47, respectively, and no relation was found...... these interactions and the clinical importance of the tissue levels of uPA, PAI-1 and uPA-PAI-1 complex, the results suggest further exploratory studies of the components in pulmonary adenocarcinomas and other cancers....

  4. The catalytic subunit of human protein kinase CK2 structurally deviates from its maize homologue in complex with the nucleotide competitive inhibitor emodin

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Klopffleisch, Karsten; Issinger, Olaf-Georg;

    2008-01-01

    biological research, and small organic inhibitors addressing CK2 are of considerable interest. We describe here the complex structure between a C-terminal deletion mutant of human CK2alpha and the ATP-competitive inhibitor emodin (1,3,8-trihydroxy-6-methylanthraquinone, International Union of Pure...

  5. Spatially localized attacks on interdependent networks: the existence of a finite critical attack size

    CERN Document Server

    Berezin, Yehiel; Danziger, Michael M; Li, Daqing; Havlin, Shlomo

    2013-01-01

    Many real world complex systems such as infrastructure, communication and transportation networks are embedded in space, where entities of one system may depend on entities of other systems. These systems are subject to geographically localized failures due to malicious attacks or natural disasters. Here we study the resilience of a system composed of two interdependent spatially embedded networks to localized geographical attacks. We find that if an attack is larger than a finite (zero fraction of the system) critical size, it will spread through the entire system and lead to its complete collapse. If the attack is below the critical size, it will remain localized. In contrast, under random attack a finite fraction of the system needs to be removed to initiate system collapse. We present both numerical simulations and a theoretical approach to analyze and predict the effect of local attacks and the critical attack size. Our results demonstrate the high risk of local attacks on interdependent spatially embedd...

  6. Bimolecular Complementation to Visualize Filovirus VP40-Host Complexes in Live Mammalian Cells: Toward the Identification of Budding Inhibitors

    Directory of Open Access Journals (Sweden)

    Yuliang Liu

    2011-01-01

    Full Text Available Virus-host interactions play key roles in promoting efficient egress of many RNA viruses, including Ebola virus (EBOV or “e” and Marburg virus (MARV or “m”. Late- (L- domains conserved in viral matrix proteins recruit specific host proteins, such as Tsg101 and Nedd4, to facilitate the budding process. These interactions serve as attractive targets for the development of broad-spectrum budding inhibitors. A major gap still exists in our understanding of the mechanism of filovirus budding due to the difficulty in detecting virus-host complexes and mapping their trafficking patterns in the natural environment of the cell. To address this gap, we used a bimolecular complementation (BiMC approach to detect, localize, and follow the trafficking patterns of eVP40-Tsg101 complexes in live mammalian cells. In addition, we used the BiMC approach along with a VLP budding assay to test small molecule inhibitors identified by in silico screening for their ability to block eVP40 PTAP-mediated interactions with Tsg101 and subsequent budding of eVP40 VLPs. We demonstrated the potential broad spectrum activity of a lead candidate inhibitor by demonstrating its ability to block PTAP-dependent binding of HIV-1 Gag to Tsg101 and subsequent egress of HIV-1 Gag VLPs.

  7. Structural and functional characterization of complex formation between two Kunitz-type serine protease inhibitors from Russell's Viper venom.

    Science.gov (United States)

    Mukherjee, Ashis K; Dutta, Sumita; Kalita, Bhargab; Jha, Deepak K; Deb, Pritam; Mackessy, Stephen P

    2016-01-01

    Snake venom Kunitz-type serine protease inhibitors (KSPIs) exhibit various biological functions including anticoagulant activity. This study elucidates the occurrence and subunit stoichiometry of a putative complex formed between two KSPIs (Rusvikunin and Rusvikunin-II) purified from the native Rusvikunin complex of Pakistan Russell's Viper (Daboia russelii russelii) venom (RVV). The protein components of the Rusvikunin complex were identified by LC-MS/MS analysis. The non-covalent interaction between two major components of the complex (Rusvikunin and Rusvikunin-II) at 1:2 stoichiometric ratio to form a stable complex was demonstrated by biophysical techniques such as spectrofluorometric, classical gel-filtration, equilibrium gel-filtration, circular dichroism (CD), dynamic light scattering (DLS), RP-HPLC and SDS-PAGE analyses. CD measurement showed that interaction between Rusvikunin and Rusvikunin-II did not change their overall secondary structure; however, the protein complex exhibited enhanced hydrodynamic diameter and anticoagulant activity as compared to the individual components of the complex. This study may lay the foundation for understanding the basis of protein complexes in snake venoms and their role in pathophysiology of snakebite.

  8. The attack navigator

    DEFF Research Database (Denmark)

    Probst, Christian W.; Willemson, Jan; Pieters, Wolter

    2016-01-01

    that are caused by the strategic behaviour of adversaries. Therefore, technology-supported methods are needed to help us identify and manage these risks. In this paper, we describe the attack navigator: a graph-based approach to security risk assessment inspired by navigation systems. Based on maps of a socio......-technical system, the attack navigator identifies routes to an attacker goal. Specific attacker properties such as skill or resources can be included through attacker profiles. This enables defenders to explore attack scenarios and the effectiveness of defense alternatives under different threat conditions....

  9. Collision Attack on the Full Extended MD4 and Pseudo-Preimage Attack on RIPEMD

    Institute of Scientific and Technical Information of China (English)

    Gao-Li Wang

    2013-01-01

    The cryptographic hash functions Extended MD4 and RIPEMD are double-branch hash functions,which consist of two parallel branches.Extended MD4 was proposed by Rivest in 1990,and RIPEMD was devised in the framework of the RIPE project (RACE Integrity Primitives Evaluation,1988~1992).On the basis of differential analysis and meet-in-the-middle attack principle,this paper proposes a collision attack on the full Extended MD4 and a pseudo-preimage attack on the full RIPEMD respectively.The collision attack on Extended MD4 holds with a complexity of 237,and a collision instance is presented.The pseudo-preimage attack on RIPEMD holds with a complexity of 2125,4,which optimizes the complexity order for brute-force attack.The results in this study will also be beneficial to the analysis of other double-branch hash functions such as RIPEMD-160.

  10. Generating IDS Attack Pattern Automatically Based on Attack Tree

    Institute of Scientific and Technical Information of China (English)

    向尕; 曹元大

    2003-01-01

    Generating attack pattern automatically based on attack tree is studied. The extending definition of attack tree is proposed. And the algorithm of generating attack tree is presented. The method of generating attack pattern automatically based on attack tree is shown, which is tested by concrete attack instances. The results show that the algorithm is effective and efficient. In doing so, the efficiency of generating attack pattern is improved and the attack trees can be reused.

  11. Structure of human Eg5 in complex with a new monastrol-based inhibitor bound in the R configuration.

    Science.gov (United States)

    Garcia-Saez, Isabel; DeBonis, Salvatore; Lopez, Roman; Trucco, Fernando; Rousseau, Bernard; Thuéry, Pierre; Kozielski, Frank

    2007-03-30

    Drugs that target mitotic spindle proteins have been proven useful for tackling tumor growth. Eg5, a kinesin-5 family member, represents a potential target, since its inhibition leads to prolonged mitotic arrest through the activation of the mitotic checkpoint and apoptotic cell death. Monastrol, a specific dihydropyrimidine inhibitor of Eg5, shows stereo-specificity, since predominantly the (S)-, but not the (R)-, enantiomer has been shown to be the biologically active compound in vitro and in cell-based assays. Here, we solved the crystal structure (2.7A) of the complex between human Eg5 and a new keto derivative of monastrol (named mon-97), a potent antimitotic inhibitor. Surprisingly, we identified the (R)-enantiomer bound in the active site, and not, as for monastrol, the (S)-enantiomer. The absolute configuration of this more active (R)-enantiomer has been unambiguously determined via chemical correlation and x-ray analysis. Unexpectedly, both the R- and the S-forms inhibit Eg5 ATPase activity with IC(50) values of 110 and 520 nM (basal assays) and 150 nm and 650 nm (microtubule-stimulated assays), respectively. However, the difference was large enough for the protein to select the (R)- over the (S)-enantiomer. Taken together, these results show that in this new monastrol family, both (R)- and (S)-enantiomers can be active as Eg5 inhibitors. This considerably broadens the alternatives for rational drug design.

  12. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Directory of Open Access Journals (Sweden)

    Andy Martens

    Full Text Available Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  13. Transforming Graphical System Models to Graphical Attack Models

    DEFF Research Database (Denmark)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, Rene Rydhof;

    2016-01-01

    Manually identifying possible attacks on an organisation is a complex undertaking; many different factors must be considered, and the resulting attack scenarios can be complex and hard to maintain as the organisation changes. System models provide a systematic representation of organisations...... that helps in structuring attack identification and can integrate physical, virtual, and social components. These models form a solid basis for guiding the manual identification of attack scenarios. Their main benefit, however, is in the analytic generation of attacks. In this work we present a systematic...... approach to transforming graphical system models to graphical attack models in the form of attack trees. Based on an asset in the model, our transformations result in an attack tree that represents attacks by all possible actors in the model, after which the actor in question has obtained the asset....

  14. Pericarditis - after heart attack

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000166.htm Pericarditis - after heart attack To use the sharing features on this page, ... occur in the days or weeks following a heart attack. Causes Two types of pericarditis can occur after ...

  15. Heart attack first aid

    Science.gov (United States)

    First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle ...

  16. Ruthenium(II) polypyridyl complexes with hydrophobic ancillary ligand as Aβ aggregation inhibitors.

    Science.gov (United States)

    Vyas, Nilima A; Ramteke, Shefali N; Kumbhar, Avinash S; Kulkarni, Prasad P; Jani, Vinod; Sonawane, Uddhavesh B; Joshi, Rajendra R; Joshi, Bimba; Erxleben, Andrea

    2016-10-01

    The synthesis, spectral and electrochemical characterization of the complexes of the type [Ru(NN)2(txbg)](2+) where NN is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), dipyrido [3,2-d:2',3f] quinoxaline (dpq) (3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4) which incorporate the tetra-xylene bipyridine glycoluril (txbg) as the ancillary ligand are described in detail. Crystal structures of ligand txbg and complex 2 were solved by single crystal X-ray diffraction. Thioflavin T (ThT) fluorescence and Transmission Electron Microscopy (TEM) results indicated that at micromolar concentration all complexes exhibit significant potential of Aβ aggregation inhibition, while the ligand txbg displayed weak activity towards Aβ aggregation. Complex 1 showed relatively low inhibition (70%) while complexes 2-4 inhibited nearly 100% Aβ aggregation after 240 h of incubation. The similar potential of complexes 2-4 and absence of any trend in their activity with the planarity of polypyridyl ligands suggests there is no marked effect of planarity of coligands on their inhibitory potential. Further studies on acetylcholinesterase (AChE) inhibition indicated very weak activity of these complexes against AChE. Detailed interactions of Aβ with both ligand and complex 2 have been studied by molecular modeling. Complex 2 showed interactions involving all three polypyridyl ligands with hydrophobic region of Aβ. Furthermore, the toxicity of these complexes towards human neuroblastoma cells was evaluated by MTT assay and except complex 4, the complexes displayed very low toxicity. PMID:27406812

  17. Heteroskorpionate Ligands In Coordination Chemistry – Complexes Relevant To Hydrogenation Catalysis, Olefine Epoxidation, And Inhibitor Studies

    OpenAIRE

    Tampier, Stefan

    2012-01-01

    This work focuses on (i) the syntheses and characterisations of various ruthenium(II) complexes bearing the bdmpza ligand, (ii) complexes based on the new bis(3,5-di-tert-butylpyrazol-1-yl)dithioacetato ligand, (iii) complexes based on bispyrazolylacetate esters, and (iv) the syntheses and characteristics of ferrocenyl-substituted ligands derived from bispyrazolylacetic acid and related chelating ligands. Chapter 3.1.2 outlines principle substitution reactions of [Ru(bdmpza)Cl(PPh3)2] (1) [bd...

  18. Pyrithione-based ruthenium complexes as inhibitors of aldo-keto reductase 1C enzymes and anticancer agents.

    Science.gov (United States)

    Kljun, Jakob; Anko, Maja; Traven, Katja; Sinreih, Maša; Pavlič, Renata; Peršič, Špela; Ude, Žiga; Codina, Elisa Esteve; Stojan, Jure; Lanišnik Rižner, Tea; Turel, Iztok

    2016-08-01

    Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo-keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range. PMID:27357845

  19. Structural studies of β-carbonic anhydrase from the green alga Coccomyxa: inhibitor complexes with anions and acetazolamide.

    Directory of Open Access Journals (Sweden)

    Shenghua Huang

    Full Text Available The β-class carbonic anhydrases (β-CAs are widely distributed among lower eukaryotes, prokaryotes, archaea, and plants. Like all CAs, the β-enzymes catalyze an important physiological reaction, namely the interconversion between carbon dioxide and bicarbonate. In plants the enzyme plays an important role in carbon fixation and metabolism. To further explore the structure-function relationship of β-CA, we have determined the crystal structures of the photoautotroph unicellular green alga Coccomyxa β-CA in complex with five different inhibitors: acetazolamide, thiocyanate, azide, iodide, and phosphate ions. The tetrameric Coccomyxa β-CA structure is similar to other β-CAs but it has a 15 amino acid extension in the C-terminal end, which stabilizes the tetramer by strengthening the interface. Four of the five inhibitors bind in a manner similar to what is found in complexes with α-type CAs. Iodide ions, however, make contact to the zinc ion via a zinc-bound water molecule or hydroxide ion--a type of binding mode not previously observed in any CA. Binding of inhibitors to Coccomyxa β-CA is mediated by side-chain movements of the conserved residue Tyr-88, extending the width of the active site cavity with 1.5-1.8 Å. Structural analysis and comparisons with other α- and β-class members suggest a catalytic mechanism in which the movements of Tyr-88 are important for the CO(2-HCO(3(- interconversion, whereas a structurally conserved water molecule that bridges residues Tyr-88 and Gln-38, seems important for proton transfer, linking water molecules from the zinc-bound water to His-92 and buffer molecules.

  20. Structural studies of β-carbonic anhydrase from the green alga Coccomyxa: inhibitor complexes with anions and acetazolamide.

    Science.gov (United States)

    Huang, Shenghua; Hainzl, Tobias; Grundström, Christin; Forsman, Cecilia; Samuelsson, Göran; Sauer-Eriksson, A Elisabeth

    2011-01-01

    The β-class carbonic anhydrases (β-CAs) are widely distributed among lower eukaryotes, prokaryotes, archaea, and plants. Like all CAs, the β-enzymes catalyze an important physiological reaction, namely the interconversion between carbon dioxide and bicarbonate. In plants the enzyme plays an important role in carbon fixation and metabolism. To further explore the structure-function relationship of β-CA, we have determined the crystal structures of the photoautotroph unicellular green alga Coccomyxa β-CA in complex with five different inhibitors: acetazolamide, thiocyanate, azide, iodide, and phosphate ions. The tetrameric Coccomyxa β-CA structure is similar to other β-CAs but it has a 15 amino acid extension in the C-terminal end, which stabilizes the tetramer by strengthening the interface. Four of the five inhibitors bind in a manner similar to what is found in complexes with α-type CAs. Iodide ions, however, make contact to the zinc ion via a zinc-bound water molecule or hydroxide ion--a type of binding mode not previously observed in any CA. Binding of inhibitors to Coccomyxa β-CA is mediated by side-chain movements of the conserved residue Tyr-88, extending the width of the active site cavity with 1.5-1.8 Å. Structural analysis and comparisons with other α- and β-class members suggest a catalytic mechanism in which the movements of Tyr-88 are important for the CO(2)-HCO(3)(-) interconversion, whereas a structurally conserved water molecule that bridges residues Tyr-88 and Gln-38, seems important for proton transfer, linking water molecules from the zinc-bound water to His-92 and buffer molecules. PMID:22162771

  1. Crystallization and preliminary crystallographic data for a ternary complex between tissue factor, factor VIIa and a BPTI-derived inhibitor

    Science.gov (United States)

    Stura, Enrico A.; Ruf, Wolfram; Wilson, Ian A.

    1996-10-01

    The binding of tissue factor (TF) with the serine protease coagulation factor VIIa (VIIa) is the initial trigger for activation of the coagulation protease cascades. In complex with TF, VIIa has profoundly enhanced function in the limited proteolytic activation of the natural substrate factors X and IX. Here we report the screening and identification of crystallization conditions to produce diffraction quality crystals of the complex between TF · VIIa and a potent inhibitor (5L 15) derived from mutagenesis of the bovine pancreatic trypsin inhibitor (BPTI) sequence. The complex crystals were obtained from the soluble extracellular domain of tissue factor, expressed in Escherichia coli as a fusion protein, VIIa expressed in mammalian cells and recombinant 5L15. Because only 1.5 mg of complex were available for this work, a reverse screening based strategy was used in the search and optimization of the crystallization conditions. Two different crystal forms were obtained from polyethylene glycol 4000 and monomethyl polyethylene glycol 2000 with cacodylate buffer at pH 6.5 in the presence of sodium and calcium ions. The addition of magnesium and zinc have profound effects on the crystallization. Both crystal forms are trigonal with cell parameters a = b = 129.3 Å, c = 110.8 Å and a = b = 67.2 Å, c = 314.8 Å diffracting to 7 and 3.2 Å resolution, respectively, each with one molecule in the asymmetric unit. Complete data sets have been collected from each of these forms to the resolution to which the crystals diffract. A structural understanding of the interaction of VIIa with its cofactor TF to form a binary enzyme, and its inhibition by 5L15 will provide a basis for the development of antithrombotic strategies.

  2. Stability of the human Hsp90-p50Cdc37 chaperone complex against nucleotides and Hsp90 inhibitors, and the influence of phosphorylation by casein kinase 2.

    Science.gov (United States)

    Olesen, Sanne H; Ingles, Donna J; Zhu, Jin-Yi; Martin, Mathew P; Betzi, Stephane; Georg, Gunda I; Tash, Joseph S; Schönbrunn, Ernst

    2015-01-19

    The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands.

  3. Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2

    Directory of Open Access Journals (Sweden)

    Sanne H. Olesen

    2015-01-01

    Full Text Available The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein–protein interaction (PPI inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2 did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM, while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands.

  4. Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2

    Science.gov (United States)

    Olesen, Sanne H.; Ingles, Donna J.; Zhu, Jin-Yi; Martin, Mathew P.; Betzi, Stephane; Georg, Gunda I.; Tash, Joseph S.; Schönbrunn, Ernst

    2015-01-01

    The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in-vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands. PMID:25608045

  5. Composite Dos Attack Model

    Directory of Open Access Journals (Sweden)

    Simona Ramanauskaitė

    2012-04-01

    Full Text Available Preparation for potential threats is one of the most important phases ensuring system security. It allows evaluating possible losses, changes in the attack process, the effectiveness of used countermeasures, optimal system settings, etc. In cyber-attack cases, executing real experiments can be difficult for many reasons. However, mathematical or programming models can be used instead of conducting experiments in a real environment. This work proposes a composite denial of service attack model that combines bandwidth exhaustion, filtering and memory depletion models for a more real representation of similar cyber-attacks. On the basis of the introduced model, different experiments were done. They showed the main dependencies of the influence of attacker and victim’s properties on the success probability of denial of service attack. In the future, this model can be used for the denial of service attack or countermeasure optimization.

  6. Seven Deadliest Network Attacks

    Energy Technology Data Exchange (ETDEWEB)

    Prowell, Stacy J [ORNL; Borkin, Michael [None; Kraus, Robert [Solutionary, Inc.

    2010-05-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting networks? Then you need "Seven Deadliest Network Attacks". This book pinpoints the most dangerous hacks and exploits specific to networks, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks detailed in this book include: Denial of Service; War Dialing; Penetration 'Testing'; Protocol Tunneling; Spanning Tree Attacks; Man-in-the-Middle; and, Password Replay. Knowledge is power, find out about the most dominant attacks currently waging war on computers and networks globally. Discover the best ways to defend against these vicious attacks; step-by-step instruction shows you how. Institute countermeasures, don't be caught defenseless again, learn techniques to make your computer and network impenetrable.

  7. FAST CORRELATION ATTACKS ON BLUETOOTH COMBINER

    Institute of Scientific and Technical Information of China (English)

    Ma Weiju; Feng Dengguo

    2006-01-01

    A simple fast correlation attack is used to analysis the security of Bluetooth combiner in this paper.This attack solves the tradeoff between the length of the keystream and the computing complexity needed to recover the secret key. We give the computing complexities of the attack algorithm according to different lengths of the known keystream. The result is less time-consuming than before. It is also shown that the security of the modified Bluetooth combiner by Hermelin and Nyberg is not significantly enhanced.

  8. What Is a Heart Attack?

    Science.gov (United States)

    ... from the NHLBI on Twitter. What Is a Heart Attack? Español A heart attack happens when the flow ... This Content: NEXT >> Featured Video What is a heart attack? 05/22/2014 Describes how a heart attack ...

  9. What Causes a Heart Attack?

    Science.gov (United States)

    ... from the NHLBI on Twitter. What Causes a Heart Attack? Coronary Heart Disease A heart attack happens if ... This Content: NEXT >> Featured Video What is a heart attack? 05/22/2014 Describes how a heart attack ...

  10. Life After a Heart Attack

    Science.gov (United States)

    ... from the NHLBI on Twitter. Life After a Heart Attack Many people survive heart attacks and live active, ... a few weeks. Anxiety and Depression After a Heart Attack After a heart attack, many people worry about ...

  11. Efficacy and safety of TNF-α inhibitors in refractory primary complex aphthosis

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2013-01-01

    Otherwise healthy patients with severe recurrent mucocutaneous aphthous ulcerations (complex aphthosis) may require systemic immunomodulatory therapy. However, a subset of patients remain resistant or intolerant to recommended therapeutic agents. Recently, case reports have described that tumor...

  12. Mammalian Target of Rapamycin Inhibitor Induced Complete Remission of a Recurrent Subependymal Giant Cell Astrocytoma in a Patient Without Features of Tuberous Sclerosis Complex.

    Science.gov (United States)

    Appalla, Deepika; Depalma, Andres; Calderwood, Stanley

    2016-07-01

    The majority of patients with subependymal giant cell astrocytoma (SEGA) have tuberous sclerosis complex (TSC). In such patients, the mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to induce responses. Isolated SEGA have been reported in patients without clinical or genetic features of TSC. The treatment of these patients with everolimus has not previously been reported. We treated a patient with a recurrent isolated SEGA with an mTOR inhibitor. The patient tolerated therapy well and had a sustained complete remission. MTOR inhibitors may be useful for the treatment of isolated SEGA. Further study is warranted. PMID:26929034

  13. Quantitative Verification and Synthesis of Attack-Defence Scenarios

    DEFF Research Database (Denmark)

    Aslanyan, Zaruhi; Nielson, Flemming; Parker, David

    2016-01-01

    Attack-defence trees are a powerful technique for formally evaluating attack-defence scenarios. They represent in an intuitive, graphical way the interaction between an attacker and a defender who compete in order to achieve conflicting objectives. We propose a novel framework for the formal...... analysis of quantitative properties of complex attack-defence scenarios, using an extension of attack-defence trees which models temporal ordering of actions and allows explicit dependencies in the strategies adopted by attackers and defenders. We adopt a game-theoretic approach, translating attack......-defence trees to two-player stochastic games, and then employ probabilistic model checking techniques to formally analyse these models. This provides a means to both verify formally specified security properties of the attack-defence scenarios and, dually, to synthesise strategies for attackers or defenders...

  14. Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf-DAPK Complex by Raf Inhibitor Combination Therapy.

    Science.gov (United States)

    Tsai, Yi-Ta; Chuang, Mei-Jen; Tang, Shou-Hung; Wu, Sheng-Tang; Chen, Yu-Chi; Sun, Guang-Huan; Hsiao, Pei-Wen; Huang, Shih-Ming; Lee, Hwei-Jen; Yu, Cheng-Ping; Ho, Jar-Yi; Lin, Hui-Kuan; Chen, Ming-Rong; Lin, Chung-Chih; Chang, Sun-Yran; Lin, Victor C; Yu, Dah-Shyong; Cha, Tai-Lung

    2015-09-01

    Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation.

  15. An electroblotting, two-step procedure for the detection of proteinases and the study of proteinase/inhibitor complexes in gelatin-containing polyacrylamide gels.

    Science.gov (United States)

    Visal-Shah, S; Vrain, T C; Yelle, T C; Nguyen-Quoc, B; Michaud, D

    2001-08-01

    A two-step gelatin/polyacrylamide gel electrophoresis (gelatin/PAGE) procedure was devised for the detection of proteinases and the study of proteinase/inhibitor interactions in complex biological extracts. The proteins are first resolved by sodium dodecyl sulfate (SDS)-PAGE under reducing or nonreducing conditions, and electrotransferred into a 0.75 mm-thick accompanying polyacrylamide slab gel containing 0.1% w/v porcine gelatin. The active proteinase bands are developed by a gelatin proteolysis step in the accompanying gel in the presence or absence of diagnostic proteinase inhibitors, allowing the assessment of proteinase classes and the visual discrimination of inhibitor-'sensitive' and -'insensitive' proteinases in complex extracts. Alternatively, protein extracts are preincubated with specific reversible inhibitors before electrophoresis, allowing a rapid discrimination of strong and weak interactions implicating proteinases and reversible inhibitors. In comparison with the standard gelatin/PAGE procedure, that involves copolymerization of gelatin with acrylamide in the resolving gel, this new procedure simplifies proteinase patterns, avoids overestimation of proteinase numbers in complex extracts, and allows in certain conditions the estimation of proteinase molecular weights. Stem bromelain (EC 3.4.22.32), bovine trypsin (EC 3.4.21.4), papain (EC 3.4.22.2), and the extracellular (digestive) cysteine proteinases of five herbivorous pests are used as model enzymes to illustrate the usefulness of this approach in detecting proteinases and in studying their interactions with specific proteinaceous inhibitors potentially useful in biotechnology.

  16. Novel antitumor adamantane-azole gold(I) complexes as potential inhibitors of thioredoxin reductase.

    Science.gov (United States)

    Garcia, Adriana; Machado, Rafael Carvalhaes; Grazul, Richard Michael; Lopes, Miriam Teresa Paz; Corrêa, Charlane Cimini; Dos Santos, Hélio F; de Almeida, Mauro Vieira; Silva, Heveline

    2016-04-01

    Gold complexes that could act as antitumor agents have attracted great attention. Heterocyclic compounds and their metal complexes display a broad spectrum of pharmacological properties. The present study reports the preparation and characterization of four novel gold(I) complexes containing tertiary phosphine and new ligands 5-adamantyl-1,3-thiazolidine-2-thione, 3-methyladamantane-1,3,4-oxadiazole-2-thione. Spectroscopic data suggest that gold is coordinated to the exocyclic sulfur atom in all cases, as confirmed by X-ray crystallographic data obtained for complex (1) and supported by quantum-mechanical calculations. The cytotoxicity of the compounds has been evaluated in comparison to cisplatin and auranofin in three different tumor cell lines, colon cancer (CT26WT), metastatic skin melanoma (B16F10), mammary adenocarcinoma (4T1) and kidney normal cell (BHK-21). The gold complexes were more active than their respective free ligands and able to inhibit the thioredoxin reductase (TrxR) enzyme, even in the presence of albumin. Molecular modeling studies were carried out to understand the interaction between the compounds and the TrxR enzyme, considered as a potential target for new compounds in cancer treatment. The docking results show that the adamantane ring is essential to stabilize the ligand-enzyme complex prior the formation of covalent bond with gold center. The structure of the new gold compounds was established on the basis of spectroscopic data, DFT calculations and X-ray diffraction. TrxR inhibition was evaluated and the results correlated with the assays in tumor cells, suggesting the TrxR as possible target for these compounds. PMID:26841791

  17. Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Nardou Katya

    2008-06-01

    Full Text Available Abstract Background Histone deacetylase inhibitors (HDACi are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities. Results We show here that the HDACi Sodium Butyrate (NaB, suberoylanilide hydroxamic acid (SAHA and Trichostatin A (TSA strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and BimEL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-xL, RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells. Conclusion HDACi are therefore interesting new anti-tumour agents for targeting highly malignant tumours such as NB, as these agents display a strong toxicity toward aggressive NB cells and they may possibly reduce angiogenesis by decreasing VEGF production by NB cells.

  18. Building Computer Network Attacks

    CERN Document Server

    Futoransky, Ariel; Richarte, Gerardo; Sarraute, Carlos

    2010-01-01

    In this work we start walking the path to a new perspective for viewing cyberwarfare scenarios, by introducing conceptual tools (a formal model) to evaluate the costs of an attack, to describe the theater of operations, targets, missions, actions, plans and assets involved in cyberwarfare attacks. We also describe two applications of this model: autonomous planning leading to automated penetration tests, and attack simulations, allowing a system administrator to evaluate the vulnerabilities of his network.

  19. Building Computer Network Attacks

    OpenAIRE

    Futoransky, Ariel; Notarfrancesco, Luciano; Richarte, Gerardo; Sarraute, Carlos

    2010-01-01

    In this work we start walking the path to a new perspective for viewing cyberwarfare scenarios, by introducing conceptual tools (a formal model) to evaluate the costs of an attack, to describe the theater of operations, targets, missions, actions, plans and assets involved in cyberwarfare attacks. We also describe two applications of this model: autonomous planning leading to automated penetration tests, and attack simulations, allowing a system administrator to evaluate the vulnerabilities o...

  20. Structure of the catalytic domain of the Tannerella forsythia matrix metallopeptidase karilysin in complex with a tetrapeptidic inhibitor.

    Science.gov (United States)

    Guevara, Tibisay; Ksiazek, Miroslaw; Skottrup, Peter Durand; Cerdà-Costa, Núria; Trillo-Muyo, Sergio; de Diego, Iñaki; Riise, Erik; Potempa, Jan; Gomis-Rüth, F Xavier

    2013-05-01

    Karilysin is the only metallopeptidase identified as a virulence factor in the odontopathogen Tannerella forsythia owing to its deleterious effect on the host immune response during bacterial infection. The very close structural and sequence-based similarity of its catalytic domain (Kly18) to matrix metalloproteinases suggests that karilysin was acquired by horizontal gene transfer from an animal host. Previous studies by phage display identified peptides with the consensus sequence XWFPXXXGGG (single-letter amino-acid codes; X represents any residue) as karilysin inhibitors with low-micromolar binding affinities. Subsequent refinement revealed that inhibition comparable to that of longer peptides could be achieved using the tetrapeptide SWFP. To analyze its binding, the high-resolution crystal structure of the complex between Kly18 and SWFP was determined and it was found that the peptide binds to the primed side of the active-site cleft in a substrate-like manner. The catalytic zinc ion is clamped by the α-amino group and the carbonyl O atom of the serine, thus distantly mimicking the general manner of binding of hydroxamate inhibitors to metallopeptidases and contributing, together with three zinc-binding histidines from the protein scaffold, to an octahedral-minus-one metal-coordination sphere. The tryptophan side chain penetrates the deep partially water-filled specificity pocket of Kly18. Together with previous serendipitous product complexes of Kly18, the present results provide the structural determinants of inhibition of karilysin and open the field for the design of novel inhibitory strategies aimed at the treatment of human periodontal disease based on a peptidic hit molecule.

  1. Seven deadliest USB attacks

    CERN Document Server

    Anderson, Brian

    2010-01-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting USB technology? Then you need Seven Deadliest USB Attacks. This book pinpoints the most dangerous hacks and exploits specific to USB, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks detailed in this book include: USB Hacksaw USB Switchblade USB Based Virus/Malicous Code Launch USB Device Overflow RAMdum

  2. Seven Deadliest Microsoft Attacks

    CERN Document Server

    Kraus, Rob; Borkin, Mike; Alpern, Naomi

    2010-01-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting Microsoft products? Then you need Seven Deadliest Microsoft Attacks. This book pinpoints the most dangerous hacks and exploits specific to Microsoft applications, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Windows Operating System-Password AttacksActive Directory-Escalat

  3. Seven Deadliest Network Attacks

    CERN Document Server

    Prowell, Stacy; Borkin, Mike

    2010-01-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting networks? Then you need Seven Deadliest Network Attacks. This book pinpoints the most dangerous hacks and exploits specific to networks, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks detailed in this book include: Denial of Service War Dialing Penetration "Testing" Protocol Tunneling Spanning Tree At

  4. Protease inhibitors as possible pitfalls in proteomic analyses of complex biological samples

    OpenAIRE

    Clifton, James; Huang, Feilei; Rucevic, Marijana; Cao, Lulu; Hixson, Douglas; Josic, Djuro

    2011-01-01

    Sample preparation, especially protein and peptide fractionation prior to identification by mass spectrometry (MS) are typically applied to reduce sample complexity. The second key element in this process is proteolytic digestion that is performed mostly by trypsin. Optimization of this step is an important factor in order to achieve both speed and better performance of proteomic analysis, and tryptic digestion prior to the MS analysis is topic of many studies. To date, only few studies pay a...

  5. Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well?

    OpenAIRE

    Petrillo, Gianluca; Cirillo, Plinio; D’Ascoli, Greta-Luana; Maresca, Fabio; Ziviello, Francesca; Chiariello, Massimo

    2010-01-01

    Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a “protective” effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pa...

  6. Photoredox Catalysis in a Complex Pharmaceutical Setting: Toward the Preparation of JAK2 Inhibitor LY2784544

    OpenAIRE

    Douglas, James J.; Cole, Kevin P.; Stephenson, Corey R J

    2014-01-01

    We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N...

  7. Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A resolution.

    Science.gov (United States)

    Pavão, F; Castilho, M S; Pupo, M T; Dias, R L A; Correa, A G; Fernandes, J B; da Silva, M F G F; Mafezoli, J; Vieira, P C; Oliva, G

    2002-06-01

    The structure of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X-ray crystallography to 1.95 A resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed. PMID:12044862

  8. Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

    Directory of Open Access Journals (Sweden)

    Mukhopadhayay Bishnu P

    2001-09-01

    Full Text Available Abstract Background This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition. Results The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S2-P2 and S3-P3 pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition. Conclusion The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (Pn...H2O....Sn of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.

  9. Situational awareness of a coordinated cyber attack

    Science.gov (United States)

    Sudit, Moises; Stotz, Adam; Holender, Michael

    2005-03-01

    As technology continues to advance, services and capabilities become computerized, and an ever increasing amount of business is conducted electronically the threat of cyber attacks gets compounded by the complexity of such attacks and the criticality of the information which must be secured. A new age of virtual warfare has dawned in which seconds can differentiate between the protection of vital information and/or services and a malicious attacker attaining their goal. In this paper we present a novel approach in the real-time detection of multistage coordinated cyber attacks and the promising initial testing results we have obtained. We introduce INFERD (INformation Fusion Engine for Real-time Decision-making), an adaptable information fusion engine which performs fusion at levels zero, one, and two to provide real-time situational assessment and its application to the cyber domain in the ECCARS (Event Correlation for Cyber Attack Recognition System) system. The advantages to our approach are fourfold: (1) The complexity of the attacks which we consider, (2) the level of abstraction in which the analyst interacts with the attack scenarios, (3) the speed at which the information fusion is presented and performed, and (4) our disregard for ad-hoc rules or a priori parameters.

  10. A NEW METHOD FOR RESYNCHRONIZATION ATTACK

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper presents a new method for resynchronization attack, which is the combination of the differential cryptanalysis and algebraic attack. By using the new method one gets a system of linear equations or low-degree equations about initial keys, and the solution of the system of equations results in the recovery of the initial keys. This method has a lower computational complexity and better performance of attack in contrast to the known methods. Accordingly, the design of the resynchronization stream generators should be reconsidered to make them strong enough to avoid our attacks. When implemented to the Toyocrypt, our method gains the computational complexity of O(217), and that of O(267) for LILI-128.

  11. Optimizing Decision Tree Attack on CAS Scheme

    Directory of Open Access Journals (Sweden)

    PERKOVIC, T.

    2016-05-01

    Full Text Available In this paper we show a successful side-channel timing attack on a well-known high-complexity cognitive authentication (CAS scheme. We exploit the weakness of CAS scheme that comes from the asymmetry of the virtual interface and graphical layout which results in nonuniform human behavior during the login procedure, leading to detectable variations in user's response times. We optimized a well-known probabilistic decision tree attack on CAS scheme by introducing this timing information into the attack. We show that the developed classifier could be used to significantly reduce the number of login sessions required to break the CAS scheme.

  12. Crystallization and Preliminary Diffraction Analysis of the CAL PDZ Domain in Complex with a Selective Peptide Inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    J Amacher; P Cushing; J Weiner; D Madden

    2011-12-31

    Cystic fibrosis (CF) is associated with loss-of-function mutations in the CF transmembrane conductance regulator (CFTR), which regulates epithelial fluid and ion homeostasis. The CFTR cytoplasmic C-terminus interacts with a number of PDZ (PSD-95/Dlg/ZO-1) proteins that modulate its intracellular trafficking and chloride-channel activity. Among these, the CFTR-associated ligand (CAL) has a negative effect on apical-membrane expression levels of the most common disease-associated mutant {Delta}F508-CFTR, making CAL a candidate target for the treatment of CF. A selective peptide inhibitor of the CAL PDZ domain (iCAL36) has recently been developed and shown to stabilize apical expression of {Delta}F508-CFTR, enhancing net chloride-channel activity, both alone and in combination with the folding corrector corr-4a. As a basis for structural studies of the CAL-iCAL36 interaction, a purification protocol has been developed that increases the oligomeric homogeneity of the protein. Here, the cocrystallization of the complex in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 35.9, b = 47.7, c = 97.3 {angstrom}, is reported. The crystals diffracted to 1.4 {angstrom} resolution. Based on the calculated Matthews coefficient (1.96 {angstrom}{sup 3} Da{sup -1}), it appears that the asymmetric unit contains two complexes.

  13. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy.

    LENUS (Irish Health Repository)

    Wander, Seth A

    2011-04-01

    Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

  14. Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Qiuxiang; Zhu, Ya; Li, Jian; Chen, Zhuxi; Han, Gye Won; Kufareva, Irina; Li, Tingting; Ma, Limin; Fenalti, Gustavo; Li, Jing; Zhang, Wenru; Xie, Xin; Yang, Huaiyu; Jiang, Hualiang; Cherezov, Vadim; Liu, Hong; Stevens, Raymond C.; Zhao, Qiang; Wu, Beili [Scripps; (Chinese Aca. Sci.); (UCSD)

    2013-10-21

    The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom–resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor–gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.

  15. Photoredox catalysis in a complex pharmaceutical setting: toward the preparation of JAK2 inhibitor LY2784544.

    Science.gov (United States)

    Douglas, James J; Cole, Kevin P; Stephenson, Corey R J

    2014-12-01

    We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N-methyl substituted tertiary amines, and therefore it represents an attractive tool for medicinal chemistry. Furthermore, a number of other interesting photoredox reactions were discovered during the course of this investigation, such as a formal methylation reaction via C-N bond cleavage, functionalization of C-H bonds alpha to amides, and a visible light-mediated iminium ion reduction. PMID:25356724

  16. Visualizing active enzyme complexes using a photoreactive inhibitor for proximity ligation--application on γ-secretase.

    Directory of Open Access Journals (Sweden)

    Sophia Schedin-Weiss

    Full Text Available Here, we present a highly sensitive method to study protein-protein interactions and subcellular location selectively for active multicomponent enzymes. We apply the method on γ-secretase, the enzyme complex that catalyzes the cleavage of the amyloid precursor protein (APP to generate amyloid β-peptide (Aβ, the major causative agent in Alzheimer disease (AD. The novel assay is based on proximity ligation, which can be used to study protein interactions in situ with very high sensitivity. In traditional proximity ligation assay (PLA, primary antibody recognition is typically accompanied by oligonucleotide-conjugated secondary antibodies as detection probes. Here, we first performed PLA experiments using antibodies against the γ-secretase components presenilin 1 (PS1, containing the catalytic site residues, and nicastrin, suggested to be involved in substrate recognition. To selectively study the interactions of active γ-secretase, we replaced one of the primary antibodies with a photoreactive γ-secretase inhibitor containing a PEG linker and a biotin group (GTB, and used oligonucleotide-conjugated streptavidin as a probe. Interestingly, significantly fewer interactions were detected with the latter, novel, assay, which is a reasonable finding considering that a substantial portion of PS1 is inactive. In addition, the PLA signals were located more peripherally when GTB was used instead of a PS1 antibody, suggesting that γ-secretase matures distal from the perinuclear ER region. This novel technique thus enables highly sensitive protein interaction studies, determines the subcellular location of the interactions, and differentiates between active and inactive γ-secretase in intact cells. We suggest that similar PLA assays using enzyme inhibitors could be useful also for other enzyme interaction studies.

  17. Modelling Social-Technical Attacks with Timed Automata

    DEFF Research Database (Denmark)

    David, Nicolas; David, Alexandre; Hansen, Rene Rydhof;

    2015-01-01

    Attacks on a system often exploit vulnerabilities that arise from human behaviour or other human activity. Attacks of this type, so-called socio-technical attacks, cover everything from social engineering to insider attacks, and they can have a devastating impact on an unprepared organisation....... In this paper we develop an approach towards modelling socio-technical systems in general and socio-technical attacks in particular, using timed automata and illustrate its application by a complex case study. Thanks to automated model checking and automata theory, we can automatically generate possible attacks...... in our model and perform analysis and simulation of both model and attack, revealing details about the specific interaction between attacker and victim. Using timed automata also allows for intuitive modelling of systems, in which quantities like time and cost can be easily added and analysed....

  18. High resolution crystal structure of rat long chain hydroxy acid oxidase in complex with the inhibitor 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1, 2, 3-thiadiazole. Implications for inhibitor specificity and drug design

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi-wei; Vignaud, Caroline; Jaafar, Adil; Lévy, Bernard; Guéritte, Françoise; Guénard, Daniel; Lederer, Florence; Mathews, F. Scott (CNRS-UMR); (WU-MED)

    2012-05-24

    Long chain hydroxy acid oxidase (LCHAO) is responsible for the formation of methylguanidine, a toxic compound with elevated serum levels in patients with chronic renal failure. Its isozyme glycolate oxidase (GOX), has a role in the formation of oxalate, which can lead to pathological deposits of calcium oxalate, in particular in the disease primary hyperoxaluria. Inhibitors of these two enzymes may have therapeutic value. These enzymes are the only human members of the family of FMN-dependent L-2-hydroxy acid-oxidizing enzymes, with yeast flavocytochrome b{sub 2} (Fcb2) among its well studied members. We screened a chemical library for inhibitors, using in parallel rat LCHAO, human GOX and the Fcb2 flavodehydrogenase domain (FDH). Among the hits was an inhibitor, CCPST, with an IC{sub 50} in the micromolar range for all three enzymes. We report here the crystal structure of a complex between this compound and LCHAO at 1.3 {angstrom} resolution. In comparison with a lower resolution structure of this enzyme, binding of the inhibitor induces a conformational change in part of the TIM barrel loop 4, as well as protonation of the active site histidine. The CCPST interactions are compared with those it forms with human GOX and those formed by two other inhibitors with human GOX and spinach GOX. These compounds differ from CCPST in having the sulfur replaced with a nitrogen in the five-membered ring as well as different hydrophobic substituents. The possible reason for the {approx}100-fold difference in affinity between these two series of inhibitors is discussed. The present results indicate that specificity is an issue in the quest for therapeutic inhibitors of either LCHAO or GOX, but they may give leads for this quest.

  19. Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids.

    Science.gov (United States)

    Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A; Silva, K Ishara; Huang, Zhentai; Amoscato, Andrew A; Peterson, James; Garapati, Venkata Krishna; Saxena, Sunil; Bayir, Hülya; Atkinson, Jeffrey; Bahar, Ivet; Kagan, Valerian E

    2014-06-01

    Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency. PMID:24631490

  20. Synthesis of novel p-tert-butylcalix[4]arene Schiff bases and their complexes with C60, potential HIV-Protease inhibitors

    Science.gov (United States)

    Khadra, Khalid Abu; Mizyed, Shehadeh; Marji, Deeb; Haddad, Salim F.; Ashram, Muhammad; Foudeh, Ayat

    2015-02-01

    Some p-tert-butylcalix[4]arene Schiff base crown ethers were synthesized, characterized using 1H, 13C-NMR, DEPT 135 and Mass spectrometry. Their complexes with C60 were isolated and characterized. The inhibition effect of these complexes on HIVP was studied and found that complexes of 9 and 10 have comparable Ki values to Pepstatine which is known as HIVP inhibitor and used as a control. The synthesis of the ligands, complexes and the inhibition behavior are discussed in this article.

  1. Complexes With Biologically Active Ligands. Part 4. Coordination Compounds of Chlorothiazide With Transition Metal Ions Behave as Strong Carbonic Anhydrase Inhibitors

    OpenAIRE

    Supuran, Claudiu T.

    1996-01-01

    Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl- 1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of carbonic anhydrase (CA).

  2. Nocturnal panic attacks

    Directory of Open Access Journals (Sweden)

    Lopes Fabiana L.

    2002-01-01

    Full Text Available The panic-respiration connection has been presented with increasing evidences in the literature. We report three panic disorder patients with nocturnal panic attacks with prominent respiratory symptoms, the overlapping of the symptoms with the sleep apnea syndrome and a change of the diurnal panic attacks, from spontaneous to situational pattern. The implication of these findings and awareness to the distinct core of the nocturnal panic attacks symptoms may help to differentiate them from sleep disorders and the search for specific treatment.

  3. Signs of a Heart Attack

    Science.gov (United States)

    ... attack Heart Health and Stroke Signs of a heart attack Related information Make the Call. Don't Miss ... to top More information on Signs of a heart attack Read more from womenshealth.gov Make the Call, ...

  4. Heart Attack Payment - Hospital

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – provider data. This data set includes provider data for payments associated with a 30-day episode of care for heart...

  5. Heart Attack Payment - State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – state data. This data set includes state-level data for payments associated with a 30-day episode of care for heart...

  6. Heart Attack Payment - National

    Data.gov (United States)

    U.S. Department of Health & Human Services — Payment for heart attack patients measure – national data. This data set includes national-level data for payments associated with a 30-day episode of care for...

  7. Transient Ischemic Attack

    Medline Plus

    Full Text Available ... TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an ... a short time. The only difference between a stroke and TIA is that with TIA the blockage ...

  8. Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I

    OpenAIRE

    Simmy Thomas; Natasha Sharma; Reyna Gonzalez; Peng-Wen Pao; Hofman, Florence M; Thomas C. Chen; Louie, Stan G.; Pirrung, Michael C.; Schönthal, Axel H

    2013-01-01

    Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD's a...

  9. Cooperating attackers in neural cryptography.

    Science.gov (United States)

    Shacham, Lanir N; Klein, Einat; Mislovaty, Rachel; Kanter, Ido; Kinzel, Wolfgang

    2004-06-01

    A successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The success of the advanced attacker presented here, called the "majority-flipping attacker," does not decay with the parameters of the model. This attacker's outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations.

  10. Crystallization and preliminary crystallographic analysis of 2-aminophenol 1,6-dioxygenase complexed with substrate and with an inhibitor.

    Science.gov (United States)

    Li, De-Feng; Zhang, Jia-Yue; Hou, Yanjie; Liu, Lei; Liu, Shuang-Jiang; Liu, Wei

    2012-11-01

    Dioxygen activation implemented by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Extradiol dioxygenase is the archetypal member of this superfamily and catalyzes the oxygenolytic ring opening of catechol analogues. Here, the crystallization and preliminary X-ray analysis of 2-aminophenol 1,6-dioxygenase, an enzyme representing a minor subset of extradiol dioxygenases that catalyze the fission of 2-aminophenol rather than catecholic compounds, is reported. Crystals of the holoenzyme with FeII and of complexes with the substrate 2-aminophenol and the suicide inhibitor 4-nitrocatechol were grown using the cocrystallization method under the same conditions as used for the crystallization of the apoenzyme. The crystals belonged to space group C2 and diffracted to 2.3-2.7 Å resolution; the crystal that diffracted to the highest resolution had unit-cell parameters a=270.24, b=48.39, c=108.55 Å, β=109.57°. All X-ray data sets collected from diffraction-quality crystals were suitable for structure determination.

  11. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening.

    Science.gov (United States)

    Orr, Adam L; Ashok, Deepthi; Sarantos, Melissa R; Shi, Tong; Hughes, Robert E; Brand, Martin D

    2013-12-01

    Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site I(Q)) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site I(Q). By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site I(Q) does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production under both normal and pathological conditions. PMID:23994103

  12. Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureus in complex with the potent inhibitor trimethoprim

    Energy Technology Data Exchange (ETDEWEB)

    Heaslet, Holly; Harris, Melissa; Fahnoe, Kelly; Sarver, Ronald; Putz, Henry; Chang, Jeanne; Subramanyam, Chakrapani; Barreiro, Gabriela; Miller, J. Richard; Pfizer

    2010-09-02

    Dihydrofolate reductase (DHFR) is the enzyme responsible for the NADPH-dependent reduction of 5,6-dihydrofolate to 5,6,7,8-tetrahydrofolate, an essential cofactor in the synthesis of purines, thymidylate, methionine, and other key metabolites. Because of its importance in multiple cellular functions, DHFR has been the subject of much research targeting the enzyme with anticancer, antibacterial, and antimicrobial agents. Clinically used compounds targeting DHFR include methotrexate for the treatment of cancer and diaminopyrimidines (DAPs) such as trimethoprim (TMP) for the treatment of bacterial infections. DAP inhibitors of DHFR have been used clinically for >30 years and resistance to these agents has become widespread. Methicillin-resistant Staphylococcus aureus (MRSA), the causative agent of many serious nosocomial and community acquired infections, and other gram-positive organisms can show resistance to DAPs through mutation of the chromosomal gene or acquisition of an alternative DHFR termed 'S1 DHFR.' To develop new therapies for health threats such as MRSA, it is important to understand the molecular basis of DAP resistance. Here, we report the crystal structure of the wild-type chromosomal DHFR from S. aureus in complex with NADPH and TMP. We have also solved the structure of the exogenous, TMP resistant S1 DHFR, apo and in complex with TMP. The structural and thermodynamic data point to important molecular differences between the two enzymes that lead to dramatically reduced affinity of DAPs to S1 DHFR. These differences in enzyme binding affinity translate into reduced antibacterial activity against strains of S. aureus that express S1 DHFR.

  13. Crystallisation and preliminary X-ray diffraction analysis of the protease from Southampton norovirus complexed with a Michael-acceptor inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Coates, Leighton [ORNL; Cooper, Jon [University of Southampton, England; Hussey, Robert [University of Southampton, England

    2008-01-01

    Noroviruses are the predominant cause of human epidemic nonbacterial gastroenteritis. Viral replication requires a cysteine protease that cleaves a 200 kDa viral polyprotein into its constituent functional parts. Here, the crystallization of the recombinant protease from the Southampton norovirus is described. While the native crystals were found to diffract only to medium resolution (2.9 {angstrom}), cocrystals of an inhibitor complex diffracted X-rays to 1.7 {angstrom} resolution. The polypeptide inhibitor (Ac-EFQLQ-propenyl ethyl ester) possesses an amino-acid sequence designed to match the substrate specificity of the enzyme, but was synthesized with a reactive Michael acceptor group at the C-terminal end.

  14. Biospecific haemosorbents based on proteinase inhibitor. II. Efficiency of biospecific antiproteinase haemosorbent 'Ovosorb' in complex treatment of experimental generalized purulent peritonitis and acute destructive pancreatitis in dogs.

    Science.gov (United States)

    Platé, N A; Kirkovsky, V V; Antiperovich, O F; Nicolaichik, V V; Valueva, T A; Sinilo, S B; Moin, V M; Lobacheva, G A

    1994-03-01

    The biospecific antiproteinase haemosorbent (BAH) 'Ovosorb' containing, in the bulk of polyacryamide gel, the ovomucoid from whites of duck eggs, was used for a complex treatment of the experimental generalized purulent peritonitis and acute destructive pancreatitis in dogs. The efficiency of BAH was manifested in the significant reduction of lethality of the experimental animals, a more rapid liquidation of proteinasaemia, normalization in plasma of alpha 1-proteinase inhibitor and protein metabolism. Thus, by eliminating proteinases from circulation, Ovosorb contributes to the cessation of imbalance in the proteinase-inhibitor system and is efficient in the therapy of pathological states related to this imbalance. PMID:8031989

  15. Metal Complexes of 1,3,4-Thiadiazole-2,5-Disulfonamide are Strong Dual Carbonic Anhydrase Inhibitors, although the Ligand Possesses very Weak such Properties

    Science.gov (United States)

    Supuran, Claudiu T.

    1995-01-01

    Coordination compounds of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) with 1,3,4-thiadiazole-2,5-disulfonamide as ligand were synthesized and characterized by IR and UV spectroscopy, conductimetry and thermogravimetry. The parent ligand is a very weak carbonic anhydrase (CA) inhibitor, although it constituted the lead for developing important classes of diuretics. The complex derivatives behave as much stronger CA inhibitors, with IC50 values around 10−8M against isozyme CA II, and 10−7 M against isozyme CAI. PMID:18472784

  16. Metal Complexes of 1,3,4-Thiadiazole-2,5-Disulfonamide are Strong Dual Carbonic Anhydrase Inhibitors, although the Ligand Possesses very Weak such Properties.

    Science.gov (United States)

    Supuran, C T

    1995-01-01

    Coordination compounds of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) with 1,3,4-thiadiazole-2,5-disulfonamide as ligand were synthesized and characterized by IR and UV spectroscopy, conductimetry and thermogravimetry. The parent ligand is a very weak carbonic anhydrase (CA) inhibitor, although it constituted the lead for developing important classes of diuretics. The complex derivatives behave as much stronger CA inhibitors, with IC(50) values around 10(-8)M against isozyme CA II, and 10(-7) M against isozyme CAI.

  17. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke Hansen;

    2002-01-01

    Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing...... a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes...... in the presence of 30% autologous serum. Blocking the CR2 ligand-binding site with monoclonal antibody (mAb) FE8 resulted in significant reduction (37.9+/-11.9%) in C3-fragment deposition, whereas MAC formation was only marginally affected (12.1+/-22.2% reduction). Blocking the CR1 binding-site resulted...

  18. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke;

    2002-01-01

    Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing a...... subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes in the......) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand, the...

  19. High Order Differential Attack and Trace Attack to Block Ciphers

    Institute of Scientific and Technical Information of China (English)

    HU Yupu; CHEN Kai; Xiao Guozhen

    2001-01-01

    In this paper, we prove a high or-der differential property of power function, then giverespectively high order differential attack and traceattack to block ciphers. These attacks depend onlyon block cipher's algebraic shape on GF(2n) and haveno relation with its designing structure. The condi-tions are given for both effective attacks and strengthagainst attacks.

  20. Structural Learning of Attack Vectors for Generating Mutated XSS Attacks

    OpenAIRE

    Yi-Hsun Wang; Ching-Hao Mao; Hahn-Ming Lee

    2010-01-01

    Web applications suffer from cross-site scripting (XSS) attacks that resulting from incomplete or incorrect input sanitization. Learning the structure of attack vectors could enrich the variety of manifestations in generated XSS attacks. In this study, we focus on generating more threatening XSS attacks for the state-of-the-art detection approaches that can find potential XSS vulnerabilities in Web applications, and propose a mechanism for structural learning of attack vectors with the aim of...

  1. XQuery Injection Attack and Countermeasures

    Institute of Scientific and Technical Information of China (English)

    谭玉森

    2014-01-01

    As a database that allows data to be stored in XML format, XML database suffers from some similar attacks as traditional relational database does. These attacks include injection attack by XQuey function in application software. These include BaseX, eXist and MarkLogic. In order to defeat these attacks, countermeasures are proposed.

  2. Seven Deadliest Wireless Technologies Attacks

    CERN Document Server

    Haines, Brad

    2010-01-01

    How can an information security professional keep up with all of the hacks, attacks, and exploits? One way to find out what the worst of the worst are is to read the seven books in our Seven Deadliest Attacks Series. Not only do we let you in on the anatomy of these attacks but we also tell you how to get rid of them and how to defend against them in the future. Countermeasures are detailed so that you can fight against similar attacks as they evolve. Attacks featured in this book include:Bluetooth AttacksCredit Card, Access Card, and Passport AttacksBad Encryption

  3. The kinase inhibitor SFV785 dislocates dengue virus envelope protein from the replication complex and blocks virus assembly.

    Directory of Open Access Journals (Sweden)

    Azlinda Anwar

    Full Text Available Dengue virus (DENV is the etiologic agent for dengue fever, for which there is no approved vaccine or specific anti-viral drug. As a remedy for this, we explored the use of compounds that interfere with the action of required host factors and describe here the characterization of a kinase inhibitor (SFV785, which has selective effects on NTRK1 and MAPKAPK5 kinase activity, and anti-viral activity on Hepatitis C, DENV and yellow fever viruses. SFV785 inhibited DENV propagation without inhibiting DENV RNA synthesis or translation. The compound did not cause any changes in the cellular distribution of non-structural 3, a protein critical for DENV RNA synthesis, but altered the distribution of the structural envelope protein from a reticulate network to enlarged discrete vesicles, which altered the co-localization with the DENV replication complex. Ultrastructural electron microscopy analyses of DENV-infected SFV785-treated cells showed the presence of viral particles that were distinctly different from viable enveloped virions within enlarged ER cisternae. These viral particles were devoid of the dense nucleocapsid. The secretion of the viral particles was not inhibited by SFV785, however a reduction in the amount of secreted infectious virions, DENV RNA and capsid were observed. Collectively, these observations suggest that SFV785 inhibited the recruitment and assembly of the nucleocapsid in specific ER compartments during the DENV assembly process and hence the production of infectious DENV. SFV785 and derivative compounds could be useful biochemical probes to explore the DENV lifecycle and could also represent a new class of anti-virals.

  4. Efficient Complex Surfactants from the Type of Fatty Acids as Corrosion Inhibitors for Mild Steel C1018 in CO{sub 2}-Environments

    Energy Technology Data Exchange (ETDEWEB)

    Abbasov, Vagif M.; Abd Ellatee, Hany M.; Aliyeva, Leylufer I.; Ismayilov, Ismayil T.; Qasimov, Elmar E.; Narmin, Mamedova M. [National Academy of Sciences of Azerbaijan, Baku (Azerbaijan)

    2013-02-15

    The efficiency of three complex surfactants based on sunflower oil and nitrogen containing compounds as corrosion inhibitors for mild steel in CO{sub 2}-saturated 1% NaCl solution, has been determined by weight loss and LPR corrosion rate measurements. These compounds inhibit corrosion even at very low concentrations. The inhibition process was attributed to the formation of an adsorbed film on the metal surface that protects the metal against corrosive media. The inhibition efficiency increases with increasing the concentration of the studied inhibitors. Maximum inhibition efficiency of the surfactants is observed at concentrations around its critical micellar concentration (CMC). Adsorption of complex surfactants on the mild steel surface is in agreement with the Langmuir adsorption isotherm model, and the calculated Gibbs free energy values confirm the chemical nature of the adsorption. Energy dispersive X-ray fluorescence microscopy (EDRF) observations of the electrode surface confirmed the existence of such an adsorbed film.

  5. Shark attack in Natal.

    Science.gov (United States)

    White, J A

    1975-02-01

    The injuries in 5 cases of shark attack in Natal during 1973-74 are reviewed. Experience in shark attacks in South Africa during this period is discussed (1965-73), and the value of protecting heavily utilized beaches in Natal with nets is assessed. The surgical applications of elasmobranch research at the Oceanographic Research Institute (Durban) and at the Headquarters of the Natal Anti-Shark Measures Board (Umhlanga Rocks) are described. Modern trends in the training of surf life-guards, the provision of basic equipment for primary resuscitation of casualties on the beaches, and the policy of general and local care of these patients in Natal are discussed.

  6. A dual approach to detect pharming attacks at the client-side

    OpenAIRE

    Gastellier-Prevost, Sophie; Gonzalez Granadillo, Gustavo Daniel; LAURENT, Maryline

    2011-01-01

    International audience Pharming attacks - a sophisticated version of phishing attacks - aim to steal users' credentials by redirecting them to a fraudulent website using DNS-based techniques. Pharming attacks can be performed at the client-side or into the Internet, using complex and well designed techniques that make the attack often imperceptible to the user. With the deployment of broadband connections for Internet access, personal networks are a privileged target for attackers. In this...

  7. A Fluorescence Polarization Assay for Binding to Macrophage Migration Inhibitory Factor and Crystal Structures for Complexes of Two Potent Inhibitors

    Science.gov (United States)

    2016-01-01

    Human macrophage migration inhibitory factor (MIF) is both a keto–enol tautomerase and a cytokine associated with numerous inflammatory diseases and cancer. Consistent with observed correlations between inhibition of the enzymatic and biological activities, discovery of MIF inhibitors has focused on monitoring the tautomerase activity using l-dopachrome methyl ester or 4-hydroxyphenyl pyruvic acid as substrates. The accuracy of these assays is compromised by several issues including substrate instability, spectral interference, and short linear periods for product formation. In this work, we report the syntheses of fluorescently labeled MIF inhibitors and their use in the first fluorescence polarization-based assay to measure the direct binding of inhibitors to the active site. The assay allows the accurate and efficient identification of competitive, noncompetitive, and covalent inhibitors of MIF in a manner that can be scaled for high-throughput screening. The results for 22 compounds show that the most potent MIF inhibitors bind with Kd values of ca. 50 nM; two are from our laboratory, and the other is a compound from the patent literature. X-ray crystal structures for two of the most potent compounds bound to MIF are also reported here. Striking combinations of protein–ligand hydrogen bonding, aryl–aryl, and cation−π interactions are responsible for the high affinities. A new chemical series was then designed using this knowledge to yield two more strong MIF inhibitors/binders. PMID:27299179

  8. Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells.

    Science.gov (United States)

    Jiang, Suhua; Zou, Zhengzhi; Nie, Peipei; Wen, Ruiling; Xiao, Yingying; Tang, Jun

    2015-01-01

    Cancer metabolism has greatly interested researchers. Mammalian target of rapamycin (mTOR) is dysregulated in a variety of cancers and considered to be an appealing therapeutic target. It has been proven that growth factor signal, mediated by mTOR complex 1 (mTORC1), drives cancer metabolism by regulating key enzymes in metabolic pathways. However, the role of mTORC2 in cancer metabolism has not been thoroughly investigated. In this study, by employing automated spectrophotometry, we found the level of glucose uptake was decreased in non-small-cell lung carcinoma (NSCLC) A549, PC-9 and SK-MES-1 cells treated with rapamycin or siRNA against Raptor, indicating that the inhibition of mTORC1 attenuated glycolytic metabolism in NSCLC cells. Moreover, the inhibition of AKT reduced glucose uptake in the cells as well, suggesting the involvement of AKT pathway in mTORC1 mediated glycolytic metabolism. Furthermore, our results showed a significant decrease in glucose uptake in rictor down-regulated NSCLC cells, implying a critical role of mTORC2 in NSCLC cell glycolysis. In addition, the experiments for MTT, ATP, and clonogenic assays demonstrated a reduction in cell proliferation, cell viability, and colony forming ability in mTOR inhibiting NSCLC cells. Interestingly, the combined application of mTORC1/2 inhibitors and glycolysis inhibitor not only suppressed the cell proliferation and colony formation, but also induced cell apoptosis, and such an effect of the combined application was stronger than that caused by mTORC1/2 inhibitors alone. In conclusion, this study reports a novel effect of mTORC2 on NSCLC cell metabolism, and reveals the synergistic effects between mTOR complex 1/2 and glycolysis inhibitors, suggesting that the combined application of mTORC1/2 and glycolysis inhibitors may be a new promising approach to treat NSCLC.

  9. Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Suhua Jiang

    Full Text Available Cancer metabolism has greatly interested researchers. Mammalian target of rapamycin (mTOR is dysregulated in a variety of cancers and considered to be an appealing therapeutic target. It has been proven that growth factor signal, mediated by mTOR complex 1 (mTORC1, drives cancer metabolism by regulating key enzymes in metabolic pathways. However, the role of mTORC2 in cancer metabolism has not been thoroughly investigated. In this study, by employing automated spectrophotometry, we found the level of glucose uptake was decreased in non-small-cell lung carcinoma (NSCLC A549, PC-9 and SK-MES-1 cells treated with rapamycin or siRNA against Raptor, indicating that the inhibition of mTORC1 attenuated glycolytic metabolism in NSCLC cells. Moreover, the inhibition of AKT reduced glucose uptake in the cells as well, suggesting the involvement of AKT pathway in mTORC1 mediated glycolytic metabolism. Furthermore, our results showed a significant decrease in glucose uptake in rictor down-regulated NSCLC cells, implying a critical role of mTORC2 in NSCLC cell glycolysis. In addition, the experiments for MTT, ATP, and clonogenic assays demonstrated a reduction in cell proliferation, cell viability, and colony forming ability in mTOR inhibiting NSCLC cells. Interestingly, the combined application of mTORC1/2 inhibitors and glycolysis inhibitor not only suppressed the cell proliferation and colony formation, but also induced cell apoptosis, and such an effect of the combined application was stronger than that caused by mTORC1/2 inhibitors alone. In conclusion, this study reports a novel effect of mTORC2 on NSCLC cell metabolism, and reveals the synergistic effects between mTOR complex 1/2 and glycolysis inhibitors, suggesting that the combined application of mTORC1/2 and glycolysis inhibitors may be a new promising approach to treat NSCLC.

  10. Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1β

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Li; DeRider, Michele; McCornack, Milissa A.; Jao, Chris; Isern, Nancy G.; Ness, Traci; Moyer, Richard; Liwang, Patricia J.

    2006-09-19

    Chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both the immune response and inflammation-related diseases. The poxvirus-encoded viral CC chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting as a potent inhibitor of chemokine action. We have used heteronuclear multidimensional NMR to determine the first structure of an orthopoxvirus vCCI in complex with a human CC chemokine MIP-1β. vCCI binds to the chemokine with 1:1 stoichiometry, using residues from its β-sheet II to interact with the a surface of MIP-1β that includes the N-terminus, the following residues in the so-called N-loop20’s region, and the 40’s loop. This structure reveals a general strategy of vCCI for selective chemokine binding, as vCCI appears to interact most stronglyinteracts most directly with residues that are conserved among a subset of CC chemokines, but are not conservednot among the other chemokine subfamilies. This structure reveals a general strategy of vCCI for selective chemokine binding. Chemokines play critical roles in the immune system, causing chemotaxis of a variety of cells to sites of infection and inflammation, as well as mediating cell homing and immune system development 1(Baggiolini 2001). To date, about 50 chemokines have been identified, and these small proteins (7-14 kDa) are believed to function by binding with endothelial or matrix glycosaminoglycans to form a concentration gradient that is then sensed by high affinity, 7-transmembrane domain G-protein coupled chemokine receptors on the surface of immune cells surface. The chemokine system is critical for host defense in healthy individuals, butand can also lead to diseases including asthma, arthritis, and atherosclerosis in the case of malfunction, often due to inappropriate inflammation and subsequent tissue damage 2(Gerard and Rollins 2001). There are four subfamilies of chemokines, CC

  11. Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP) pathway enzyme expression in Catharanthus roseus.

    Science.gov (United States)

    Han, Mei; Heppel, Simon C; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

    2013-01-01

    In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation.

  12. Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP pathway enzyme expression in Catharanthus roseus.

    Directory of Open Access Journals (Sweden)

    Mei Han

    Full Text Available In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS, a new (type I DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR, respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms, DXR, and hydroxymethylbutenyl diphosphate synthase (HDS were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation.

  13. Enzyme Inhibitor Studies Reveal Complex Control of Methyl-D-Erythritol 4-Phosphate (MEP) Pathway Enzyme Expression in Catharanthus roseus

    Science.gov (United States)

    Han, Mei; Heppel, Simon C.; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

    2013-01-01

    In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation. PMID:23650515

  14. Improved Impossible Differential Attacks on Large-Block Rijndael

    DEFF Research Database (Denmark)

    Wang, Qingju; Gu, Dawu; Rijmen, Vincent;

    2012-01-01

    . The improvement can lead to 10-round attack on Rijndael-256 as well. With 2198.1 chosen plaintexts, an attack is demonstrated on 9-round Rijndael-224 with 2 195.2 encryptions and 2140.4 bytes memory. Increasing the data complexity to 2216 plaintexts, the time complexity can be reduced to 2130 encryptions...... and the memory requirements to 2 93.6 bytes. For 9-round Rijndael-256, we provide an attack requiring 2229.3 chosen plaintexts, 2194 encryptions, and 2 139.6 bytes memory. Alternatively, with 2245.3 plaintexts, an attack with a reduced time of 2127.1 encryptions and a memory complexity of 290.9 bytes can...... be mounted. With 2244.2 chosen plaintexts, we can attack 10-round Rijndael-256 with 2253.9 encryptions and 2186.8 bytes of memory....

  15. Structure of a small-molecule inhibitor complexed with GlmU from Haemophilus influenzae reveals an allosteric binding site

    Energy Technology Data Exchange (ETDEWEB)

    Mochalkin, Igor; Lightle, Sandra; Narasimhan, Lakshmi; Bornemeier, Dirk; Melnick, Michael; VanderRoest, Steven; McDowell, Laura (Pfizer)

    2008-04-02

    N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and an attractive target for antibiotic drug discovery. GlmU catalyzes the formation of uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolisaccharide biosynthesis in both Gram-negative and Gram-positive bacteria. Here we disclose a 1.9 {angstrom} resolution crystal structure of a synthetic small-molecule inhibitor of GlmU from Haemophilus influenzae (hiGlmU). The compound was identified through a high-throughput screening (HTS) configured to detect inhibitors that target the uridyltransferase active site of hiGlmU. The original HTS hit exhibited a modest micromolar potency (IC{sub 50} - 18 {mu}M in a racemic mixture) against hiGlmU and no activity against Staphylococcus aureus GlmU (saGlmU). The determined crystal structure indicated that the inhibitor occupies an allosteric site adjacent to the GlcNAc-1-P substrate-binding region. Analysis of the mechanistic model of the uridyltransferase reaction suggests that the binding of this allosteric inhibitor prevents structural rearrangements that are required for the enzymatic reaction, thus providing a basis for structure-guided design of a new class of mechanism-based inhibitors of GlmU.

  16. Bluetooth security attacks comparative analysis, attacks, and countermeasures

    CERN Document Server

    Haataja, Keijo; Pasanen, Sanna; Toivanen, Pekka

    2013-01-01

    This overview of Bluetooth security examines network vulnerabilities and offers a comparative analysis of recent security attacks. It also examines related countermeasures and proposes a novel attack that works against all existing Bluetooth versions.

  17. Is There Anybody There? A Psychodynamic View of Panic Attack.

    Science.gov (United States)

    Rizq, Rosemary

    2002-01-01

    Presents a process analysis of a psychodynamic intervention for a client with panic attacks. Discusses how a psychodynamic understanding of the complex etiology of the client's panic attacks that ultimately produced improved coping skills and a subjective sense of improvement for her. Process analysis is used to illustrate the theoretical base,…

  18. The LOCAL attack: Cryptanalysis of the authenticated encryption scheme ALE

    DEFF Research Database (Denmark)

    Khovratovich, Dmitry; Rechberger, Christian

    2014-01-01

    We show how to produce a forged (ciphertext, tag) pair for the scheme ALE with data and time complexity of 2102 ALE encryptions of short messages and the same number of authentication attempts. We use a differential attack based on a local collision, which exploits the availability of extracted...... state bytes to the adversary. Our approach allows for a time-data complexity tradeoff, with an extreme case of a forgery produced after 2119 attempts and based on a single authenticated message. Our attack is further turned into a state recovery and a universal forgery attack with a time complexity...

  19. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

    2016-02-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed.

  20. ATTACK PATTERNS FOR DETECTING AND PREVENTING DDOS AND REPLAY ATTACKS

    Directory of Open Access Journals (Sweden)

    A.MADHURI,

    2010-09-01

    Full Text Available In this paper, we discuss the methods for detecting and preventing the DDoS Attacks and Replay Attacks, which have been posing the problems for the Internet. We explained a scheme AMFDR (AttackPatterns for Marking Filtering DoS and Replay attacks that identifies the attack packets from the packets that are sent by legitimate users and filters the attack packets. A Denial of service attack is generally launched to make a service unavailable even to an unauthorized user. If this attack uses many computers across the world, it is called Distributed Denial of service attack. Replay attack is retransmission of a data transmission which used to gain authentication in a fraudulent manner. These replayed packets or attack packets are identified. This scheme is less expensive and the implementation of this scheme needs minimal interaction with routers. The scheme is like firewall system, so that the occurrence of an attack is recognized quickly and a punitive action is taken without any loss genuine packets.

  1. Ca2+/calmodulin-dependent kinase II contributes to inhibitor of nuclear factor-kappa B kinase complex activation in Helicobacter pylori infection.

    Science.gov (United States)

    Maubach, Gunter; Sokolova, Olga; Wolfien, Markus; Rothkötter, Hermann-Josef; Naumann, Michael

    2013-09-15

    Helicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor-kappa B (NF-κB) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H. pylori induces the NF-κB-mediated inflammatory response. In our study, we investigated the role of Ca(2+) /calmodulin-dependent kinase II (CAMKII), calmodulin, protein kinases C (PKCs) and the CARMA3-Bcl10-MALT1 (CBM) complex in conjunction with H. pylori-induced activation of NF-κB via the inhibitor of nuclear factor-kappa B kinase (IKK) complex. We use specific inhibitors and/or RNA interference to assess the contribution of these components. Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-κB in response to H. pylori infection, but not in response to TNF-α. Thus, our findings are specific for H. pylori infected cells. Neither the PKCs α, δ, θ, nor the CBM complex itself is involved in the activation of NF-κB by H. pylori. The contribution of CAMKII and calmodulin, but not PKCs/CBM to the induction of an inflammatory response by H. pylori infection augment the understanding of the molecular mechanism involved and provide potential new disease markers for the diagnosis of gastric inflammatory diseases including gastric cancer.

  2. Simulating Cyber-Attacks for Fun and Profit

    CERN Document Server

    Futoransky, Ariel; Orlicki, Jose; Sarraute, Carlos

    2010-01-01

    We introduce a new simulation platform called Insight, created to design and simulate cyber-attacks against large arbitrary target scenarios. Insight has surprisingly low hardware and configuration requirements, while making the simulation a realistic experience from the attacker's standpoint. The scenarios include a crowd of simulated actors: network devices, hardware devices, software applications, protocols, users, etc. A novel characteristic of this tool is to simulate vulnerabilities (including 0-days) and exploits, allowing an attacker to compromise machines and use them as pivoting stones to continue the attack. A user can test and modify complex scenarios, with several interconnected networks, where the attacker has no initial connectivity with the objective of the attack. We give a concise description of this new technology, and its possible uses in the security research field, such as pentesting training, study of the impact of 0-days vulnerabilities, evaluation of security countermeasures, and risk...

  3. Simultaneous Attacks by Terrorist Organisations

    Directory of Open Access Journals (Sweden)

    Kathleen Deloughery

    2013-12-01

    Full Text Available While terror attacks that are a part of a coordinated effort receive attention in the popular media, they have not received much attention in the academic literature. The decision to carry out simultaneous attacks should be examined as one of the choices a terrorist organisation makes about the method of attack. Determining the impact of simultaneous attacks vis-à-vis a single attack can explain why groups would use this method. Up to one quarter of all attacks coded in two major databases, GTD and ITERATE, may be part of a simultaneous campaign. Empirical analysis shows simultaneous attacks are more likely to be successful and cause more fatalities, though not in a one-to-one fashion. These results underline the importance of considering simultaneous attacks in empirical analysis.

  4. High-resolution crystal structure of Streptococcus pyogenes β-NAD{sup +} glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin [Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Hyoun Sook [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Sang Jae [Seoul National University, Seoul 151-742 (Korea, Republic of); Im, Ha Na; Jang, Jun Young [Seoul National University, Seoul 151-747 (Korea, Republic of); Suh, Se Won, E-mail: sewonsuh@snu.ac.kr [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-747 (Korea, Republic of)

    2013-11-01

    The crystal structure of the complex between the C-terminal domain of Streptococcus pyogenes β-NAD{sup +} glycohydrolase and an endogenous inhibitor for SPN was determined at 1.70 Å. It reveals that the interface between the two proteins is highly rich in water molecules. One of the virulence factors produced by Streptococcus pyogenes is β-NAD{sup +} glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPN{sub ct}–IFS complex, which consists of the SPN C-terminal domain (SPN{sub ct}; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPN{sub ct} and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.

  5. Key Recovery Attacks on Recent Authenticated Ciphers

    DEFF Research Database (Denmark)

    Bogdanov, Andrey; Dobraunig, Christoph; Eichlseder, Maria;

    2014-01-01

    and wireless networks. All these schemes use well-established and secure components such as the AES, Grain-like NFSRs, ChaCha and SipHash as their building blocks. However, we discover key recovery attacks for all three designs, featuring square-root complexities. Using a key collision technique, we can...... recover the secret key of AVALANCHE in 2n/2, where n 2∈ {28; 192; 256} is the key length. This technique also applies to the authentication part of Calico whose 128-bit key can be recovered in 264 time. For RBS, we can recover its full 132-bit key in 265 time with a guess-and-determine attack. All attacks...

  6. LITERATURE SURVEY ON WORMHOLE ATTACK

    OpenAIRE

    Avinash S. Bundela

    2015-01-01

    Security plays an important role in Mobile Ad Hoc Network when data transmission is performed within un - trusted wireless scenario. Various attacks like Black hole, Wormhole, Gray hole and many more have been identified & corresponding solutions have been proposed. These attacks are caused by the malicious node hence ad hoc wireless network is unprotected from the attacks of the malicious node. Between all these attacks the wormhole att ...

  7. When women attack.

    Science.gov (United States)

    McLaughlin, Bryan; Davis, Catasha; Coppini, David; Kim, Young Mie; Knisely, Sandra; McLeod, Douglas

    2015-01-01

    The common assumption that female candidates on the campaign trail should not go on the attack, because such tactics contradict gender stereotypes, has not received consistent support. We argue that in some circumstances gender stereotypes will favor female politicians going negative. To test this proposition, this study examines how gender cues affect voter reactions to negative ads in the context of a political sex scandal, a context that should prime gender stereotypes that favor females. Using an online experiment involving a national sample of U.S. adults (N = 599), we manipulate the gender and partisan affiliation of a politician who attacks a male opponent caught in a sex scandal involving sexually suggestive texting to a female intern. Results show that in the context of a sex scandal, a female candidate going on the attack is evaluated more positively than a male. Moreover, while female participants viewed the female sponsor more favorably, sponsor gender had no effect on male participants. Partisanship also influenced candidate evaluations: the Democratic female candidate was evaluated more favorably than her Republican female counterpart. PMID:26399945

  8. Localized attack on clustering networks

    CERN Document Server

    Dong, Gaogao; Du, Ruijin; Shao, Shuai; Stanley, H Eugene; Shlomo, Havlin

    2016-01-01

    Clustering network is one of which complex network attracting plenty of scholars to discuss and study the structures and cascading process. We primarily analyzed the effect of clustering coefficient to other various of the single clustering network under localized attack. These network models including double clustering network and star-like NON with clustering and random regular (RR) NON of ER networks with clustering are made up of at least two networks among which exist interdependent relation among whose degree of dependence is measured by coupling strength. We show both analytically and numerically, how the coupling strength and clustering coefficient effect the percolation threshold, size of giant component, critical coupling point where the behavior of phase transition changes from second order to first order with the increase of coupling strength between the networks. Last, we study the two types of clustering network: one type is same with double clustering network in which each subnetwork satisfies ...

  9. Crystal Structure of Barley Limit Dextrinase-Limit Dextrinase Inhibitor (LD-LDI) Complex Reveals Insights into Mechanism and Diversity of Cereal Type Inhibitors

    DEFF Research Database (Denmark)

    Møller, Marie Sofie; Vester-Christensen, Malene Bech; Jensen, Johanne M.;

    2015-01-01

    for effective inhibition of debranching enzymes having characteristic open active site architecture. The findings give a mechanistic rationale for the potency of LD activity regulation and provide a molecular understanding of the debranching events associated with optimal starch mobilization and utilization......Molecular details underlying regulation of starch mobilization in cereal seed endosperm remain unknown despite the paramount role of this process in plant growth. The structure of the complex between the starch debranching enzyme barley limit dextrinase (LD), hydrolyzing α-1,6-glucosidic linkages...... by LDI inhibition of the enzyme activity. A phylogenetic analysis identified four LDI-like proteins in cereals among the 45 sequences from monocot databases that could be classified as unique CTI sequences. The unprecedented binding mechanism shown here for LDI has likely evolved in cereals from a need...

  10. Structural Learning of Attack Vectors for Generating Mutated XSS Attacks

    Directory of Open Access Journals (Sweden)

    Yi-Hsun Wang

    2010-09-01

    Full Text Available Web applications suffer from cross-site scripting (XSS attacks that resulting from incomplete or incorrect input sanitization. Learning the structure of attack vectors could enrich the variety of manifestations in generated XSS attacks. In this study, we focus on generating more threatening XSS attacks for the state-of-the-art detection approaches that can find potential XSS vulnerabilities in Web applications, and propose a mechanism for structural learning of attack vectors with the aim of generating mutated XSS attacks in a fully automatic way. Mutated XSS attack generation depends on the analysis of attack vectors and the structural learning mechanism. For the kernel of the learning mechanism, we use a Hidden Markov model (HMM as the structure of the attack vector model to capture the implicit manner of the attack vector, and this manner is benefited from the syntax meanings that are labeled by the proposed tokenizing mechanism. Bayes theorem is used to determine the number of hidden states in the model for generalizing the structure model. The paper has the contributions as following: (1 automatically learn the structure of attack vectors from practical data analysis to modeling a structure model of attack vectors, (2 mimic the manners and the elements of attack vectors to extend the ability of testing tool for identifying XSS vulnerabilities, (3 be helpful to verify the flaws of blacklist sanitization procedures of Web applications. We evaluated the proposed mechanism by Burp Intruder with a dataset collected from public XSS archives. The results show that mutated XSS attack generation can identify potential vulnerabilities.

  11. Palladium(II) and zinc(II) complexes of neutral [N2O2] donor Schiff bases derived from furfuraldehyde: synthesis, characterization, fluorescence and corrosion inhibitors of ligands.

    Science.gov (United States)

    Ali, Omyma A M

    2014-11-11

    Metal complexes of Schiff bases derived from furfuraldehyde and 4,5-dimethyl-1,2-phenylendiamine (L1) or 4,5-dichloro-1,2-phenylendiamine (L2) have been reported and characterized based on elemental analyses, IR, 1H NMR, UV-Vis, magnetic moment, molar conductance and thermal analysis. The complexes are found to have the formulae [PdL1-2]Cl2 and [ZnL1-2](AcO)2·H2O. The molar conductance data reveal that Pd(II) and Zn(II) chelates are ionic in nature and are of the type 2:1 electrolytes. The spectral data are consistent with a square planar and tetrahedral geometry around Pd(II) and Zn(II), respectively, in which the ligands act as tetradentate ligands. The thermal behavior of some chelates is studied and the activation thermodynamic parameters are calculated using Coats-Redfern method. The corrosion inhibition of stainless steel types 410 and 304 in 1 M HCl using the synthesized Schiff bases as inhibitors have been studied by weight loss method. The obtained data considered these ligands as efficient corrosion inhibitors. The ligands and their metal complexes exhibited considerable antibacterial activity against Staphylococcusaureus, and Escherichiacoli and antifungal activity against Candida albicans.

  12. Seven Deadliest Unified Communications Attacks

    CERN Document Server

    York, Dan

    2010-01-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting Unified Communications technology? Then you need Seven Deadliest Unified Communication Attacks. This book pinpoints the most dangerous hacks and exploits specific to Unified Communications, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks featured in this book include: UC Ecosystem Attacks Insecure Endpo

  13. Crystal Structures of Human Choline Kinase Isoforms in Complex with Hemicholinium-3 Single Amino Acid near the Active Site Influences Inhibitor Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Bum Soo; Allali-Hassani, Abdellah; Tempel, Wolfram; Finerty, Jr., Patrick J.; MacKenzie, Farrell; Dimov, Svetoslav; Vedadi, Masoud; Park, Hee-Won (Toronto)

    2010-07-06

    Human choline kinase (ChoK) catalyzes the first reaction in phosphatidylcholine biosynthesis and exists as ChoK{alpha} ({alpha}1 and {alpha}2) and ChoK{beta} isoforms. Recent studies suggest that ChoK is implicated in tumorigenesis and emerging as an attractive target for anticancer chemotherapy. To extend our understanding of the molecular mechanism of ChoK inhibition, we have determined the high resolution x-ray structures of the ChoK{alpha}1 and ChoK{beta} isoforms in complex with hemicholinium-3 (HC-3), a known inhibitor of ChoK. In both structures, HC-3 bound at the conserved hydrophobic groove on the C-terminal lobe. One of the HC-3 oxazinium rings complexed with ChoK{alpha}1 occupied the choline-binding pocket, providing a structural explanation for its inhibitory action. Interestingly, the HC-3 molecule co-crystallized with ChoK{beta} was phosphorylated in the choline binding site. This phosphorylation, albeit occurring at a very slow rate, was confirmed experimentally by mass spectroscopy and radioactive assays. Detailed kinetic studies revealed that HC-3 is a much more potent inhibitor for ChoK{alpha} isoforms ({alpha}1 and {alpha}2) compared with ChoK{beta}. Mutational studies based on the structures of both inhibitor-bound ChoK complexes demonstrated that Leu-401 of ChoK{alpha}2 (equivalent to Leu-419 of ChoK{alpha}1), or the corresponding residue Phe-352 of ChoK{beta}, which is one of the hydrophobic residues neighboring the active site, influences the plasticity of the HC-3-binding groove, thereby playing a key role in HC-3 sensitivity and phosphorylation.

  14. Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.

    Science.gov (United States)

    Turrens, J F; Bickar, D; Lehninger, A L

    1986-06-01

    The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase.

  15. Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.

    Science.gov (United States)

    Turrens, J F; Bickar, D; Lehninger, A L

    1986-06-01

    The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase. PMID:3016533

  16. High-resolution complex of papain with remnants of a cysteine protease inhibitor derived from Trypanosoma brucei

    OpenAIRE

    Alphey, Magnus S.; Hunter, William N.

    2006-01-01

    Attempts to cocrystallize the cysteine protease papain derived from the latex of Carica papaya with an inhibitor of cysteine proteases (ICP) from Trypanosoma brucei were unsuccessful. However, crystals of papain that diffracted to higher resolution, 1.5 Å, than other crystals of this archetypal cysteine protease were obtained, so the analysis was continued. Surprisingly, the substrate-binding cleft was occupied by two short peptide fragments which have been assigned as remnants of ICP. Compar...

  17. Molecular dynamics simulations of sonic hedgehog-receptor and inhibitor complexes and their applications for potential anticancer agent discovery.

    Directory of Open Access Journals (Sweden)

    Swan Hwang

    Full Text Available The sonic hedgehog (Shh signaling pathway is necessary for a variety of development and differentiation during embryogenesis as well as maintenance and renascence of diverse adult tissues. However, an abnormal activation of the signaling pathway is related to various cancers. In this pathway, the Shh signaling transduction is facilitated by binding of Shh to its receptor protein, Ptch. In this study, we modeled the 3D structure of functionally important key loop peptides of Ptch based on homologous proteins. Using this loop model, the molecular interactions between the structural components present in the pseudo-active site of Shh and key residues of Ptch was investigated in atomic level through molecular dynamics (MD simulations. For the purpose of developing inhibitor candidates of the Shh signaling pathway, the Shh pseudo-active site of this interface region was selected as a target to block the direct binding between Shh and Ptch. Two different structure-based pharmacophore models were generated considering the key loop of Ptch and known inhibitor-induced conformational changes of the Shh through MD simulations. Finally two hit compounds were retrieved through a series of virtual screening combined with molecular docking simulations and we propose two hit compounds as potential inhibitory lead candidates to block the Shh signaling pathway based on their strong interactions to receptor or inhibitor induced conformations of the Shh.

  18. Structural Learning of Attack Vectors for Generating Mutated XSS Attacks

    CERN Document Server

    Wang, Yi-Hsun; Lee, Hahn-Ming; 10.4204/EPTCS.35.2

    2010-01-01

    Web applications suffer from cross-site scripting (XSS) attacks that resulting from incomplete or incorrect input sanitization. Learning the structure of attack vectors could enrich the variety of manifestations in generated XSS attacks. In this study, we focus on generating more threatening XSS attacks for the state-of-the-art detection approaches that can find potential XSS vulnerabilities in Web applications, and propose a mechanism for structural learning of attack vectors with the aim of generating mutated XSS attacks in a fully automatic way. Mutated XSS attack generation depends on the analysis of attack vectors and the structural learning mechanism. For the kernel of the learning mechanism, we use a Hidden Markov model (HMM) as the structure of the attack vector model to capture the implicit manner of the attack vector, and this manner is benefited from the syntax meanings that are labeled by the proposed tokenizing mechanism. Bayes theorem is used to determine the number of hidden states in the model...

  19. L-Ornithine Schiff base-copper and -cadmium complexes as new proteasome inhibitors and apoptosis inducers in human cancer cells.

    Science.gov (United States)

    Zhang, Zhongyu; Bi, Caifeng; Fan, Yuhua; Zhang, Nan; Deshmukh, Rahul; Yan, Xingchen; Lv, Xiuwen; Zhang, Pengfei; Zhang, Xia; Dou, Q Ping

    2015-01-01

    Ubiquitin-proteasome system (UPS) plays a crucial role in many cellular processes such as cell cycle, proliferation and apoptosis. Aberrant activation of UPS may result in cellular transformation or other altered pathological conditions. Previous studies have shown that metal-based complexes could inhibit proteasome activity and induce apoptosis in certain human cancer cells. In the current study, we report that the cadmium and copper complexes with heterocycle-ornithine Schiff base are potent inhibitors of proteasomal chymotrypsin-like (CT-like) activity, leading to induction of apoptosis in cancer cells. Two novel copper-containing complexes and two novel cadmium-containing complexes with different heterocycle-ornithine Schiff base structures as ligands were synthesized and characterized. We found that complexes Cu1, Cd1 and Cd2 show proteasome-inhibitory activities in human breast cancer MDA-MB-231 and human prostate cancer LNCaP cells, resulting in the accumulation of p27, a natural proteasome substrate and other ubiquitinated proteins, followed by the induction of apoptosis. Our results suggest that metal complexes with heterocycle-ornithine Schiff base have proteasome-inhibitory capabilities and have the potential to be developed into novel anticancer drugs.

  20. Inhibition effects of PMA/SbBr3 complex inhibitor on copper and copper-nickel alloy in LiBr solutions

    Institute of Scientific and Technical Information of China (English)

    HU Xian-qi; LIANG Cheng-hao; HUANG Nai-bao

    2005-01-01

    The effects of PMA/SbBr3 inhibitor on copper and copper-nickel alloy in 55%LiBr solution were investigated by chemical immersion and electrochemical measurements. The results indicate that in boiling 55% LiBr solution containing PMA/SbBr3 inhibitor, corrosion rates of copper and copper-nickel alloy are 67.48 μm/a and 38. 14μm/a, respectively. Since both anodic and cathodic electrochemical reactions can be inhibited, PMA/SbBr3 belongs to complex inhibitor. PMA has the effect of inhibiting hydrogen evolution and [PMo12 O40]3- , the anion of PMA,has a strong oxidizing effect. Sb3+ also shows an oxidizing effect. It may exist in LiBr solutions stably with PMA.Because of the synergistic effect of PMA and Sb3+ , a protective film, comprising CuO, Cu2O and Sb, formed on copper and copper-nickel alloy surface may prevent Br- from diffusing to the surface of metals. As a result, the anticorrosion performance of copper and copper-nickel alloy may be improved.

  1. Structure of ‘linkerless’ hydroxamic acid inhibitor-HDAC8 complex confirms the formation of an isoform-specific subpocket

    Energy Technology Data Exchange (ETDEWEB)

    Tabackman, Alexa A.; Frankson, Rochelle; Marsan, Eric S.; Perry, Kay; Cole, Kathryn E. (Ithaca); (Cornell)

    2016-10-17

    Histone deacetylases (HDACs) catalyze the hydrolysis of acetylated lysine side chains in histone and non-histone proteins, and play a critical role in the regulation of many biological processes, including cell differentiation, proliferation, senescence, and apoptosis. Aberrant HDAC activity is associated with cancer, making these enzymes important targets for drug design. In general, HDAC inhibitors (HDACi) block the proliferation of tumor cells by inducing cell differentiation, cell cycle arrest, and/or apoptosis, and comprise some of the leading therapies in cancer treatments. To date, four HDACi have been FDA approved for the treatment of cancers: suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza®), romidepsin (FK228, Istodax®), belinostat (Beleodaq®), and panobinostat (Farydak®). Most current inhibitors are pan-HDACi, and non-selectively target a number of HDAC isoforms. Six previously reported HDACi were rationally designed, however, to target a unique sub-pocket found only in HDAC8. While these inhibitors were indeed potent against HDAC8, and even demonstrated specificity for HDAC8 over HDACs 1 and 6, there were no structural data to confirm the mode of binding. Here we report the X-ray crystal structure of Compound 6 complexed with HDAC8 to 1.98 Å resolution. We also describe the use of molecular docking studies to explore the binding interactions of the other 5 related HDACi. Our studies confirm that the HDACi induce the formation of and bind in the HDAC8-specific subpocket, offering insights into isoform-specific inhibition.

  2. How to deal with weak interactions in noncovalent complexes analyzed by electrospray mass spectrometry: cyclopeptidic inhibitors of the nuclear receptor coactivator 1-STAT6.

    Science.gov (United States)

    Touboul, David; Maillard, Ludovic; Grässlin, Anja; Moumne, Roba; Seitz, Markus; Robinson, John; Zenobi, Renato

    2009-02-01

    Mass spectrometry, and especially electrospray ionization, is now an efficient tool to study noncovalent interactions between proteins and inhibitors. It is used here to study the interaction of some weak inhibitors with the NCoA-1/STAT6 protein with K(D) values in the microM range. High signal intensities corresponding to some nonspecific electrostatic interactions between NCoA-1 and the oppositely charged inhibitors were observed by nanoelectrospray mass spectrometry, due to the use of high ligand concentrations. Diverse strategies have already been developed to deal with nonspecific interactions, such as controlled dissociation in the gas phase, mathematical modeling, or the use of a reference protein to monitor the appearance of nonspecific complexes. We demonstrate here that this last methodology, validated only in the case of neutral sugar-protein interactions, i.e., where dipole-dipole interactions are crucial, is not relevant in the case of strong electrostatic interactions. Thus, we developed a novel strategy based on half-maximal inhibitory concentration (IC(50)) measurements in a competitive assay with readout by nanoelectrospray mass spectrometry. IC(50) values determined by MS were finally converted into dissociation constants that showed very good agreement with values determined in the liquid phase using a fluorescence polarization assay. PMID:18996720

  3. Practical Attacks on AES-like Cryptographic Hash Functions

    DEFF Research Database (Denmark)

    Kölbl, Stefan; Rechberger, Christian

    2015-01-01

    Despite the great interest in rebound attacks on AES-like hash functions since 2009, we report on a rather generic, albeit keyschedule-dependent, algorithmic improvement: A new message modification technique to extend the inbound phase, which even for large internal states makes it possible...... to drastically reduce the complexity of attacks to very practical values for reduced-round versions. Furthermore, we describe new and practical attacks on Whirlpool and the recently proposed GOST R hash function with one or more of the following properties: more rounds, less time/memory complexity, and more...

  4. Attacks on computer systems

    Directory of Open Access Journals (Sweden)

    Dejan V. Vuletić

    2012-01-01

    Full Text Available Computer systems are a critical component of the human society in the 21st century. Economic sector, defense, security, energy, telecommunications, industrial production, finance and other vital infrastructure depend on computer systems that operate at local, national or global scales. A particular problem is that, due to the rapid development of ICT and the unstoppable growth of its application in all spheres of the human society, their vulnerability and exposure to very serious potential dangers increase. This paper analyzes some typical attacks on computer systems.

  5. How Is a Heart Attack Treated?

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Is a Heart Attack Treated? Early treatment for a heart attack can ... or years after the procedure. Other Treatments for Heart Attack Other treatments for heart attack include: Medicines Medical ...

  6. How Is a Heart Attack Diagnosed?

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Is a Heart Attack Diagnosed? Your doctor will diagnose a heart attack ... This Content: NEXT >> Featured Video What is a heart attack? 05/22/2014 Describes how a heart attack ...

  7. Recent "phishing" attacks

    CERN Multimedia

    IT Department

    2009-01-01

    Over the last few weeks there has been a marked increase in the number of attacks on CERN made by cybercriminals. Typical attacks arrive in the form of e-mail messages purporting to come from the CERN Help Desk, Mail Service, or some similarly official-sounding entity and suggest that there is a problem with your account, such as it being over-quota. They then ask you to click on a link or to reply and give your password. Please don’t! Be cautious of any unexpected messages containing web links even if they appear to come from known contacts. If you happen to click on such a link and if your permission is requested to run or install software, always decline it. NEVER provide your password or other details if these are requested. These messages try to trick you into clicking on Web links which will help them to install malicious software on your computer, and anti-virus software cannot be relied on to detect all cases. In case of questions on this topic, you may contact mailto:helpdesk@cern.ch. CERN Comput...

  8. Fast WEP-Key Recovery Attack Using Only Encrypted IP Packets

    Science.gov (United States)

    Teramura, Ryoichi; Asakura, Yasuo; Ohigashi, Toshihiro; Kuwakado, Hidenori; Morii, Masakatu

    Conventional efficient key recovery attacks against Wired Equivalent Privacy (WEP) require specific initialization vectors or specific packets. Since it takes much time to collect the packets sufficiently, any active attack should be performed. An Intrusion Detection System (IDS), however, will be able to prevent the attack. Since the attack logs are stored at the servers, it is possible to prevent such an attack. This paper proposes an algorithm for recovering a 104-bit WEP key from any IP packets in a realistic environment. This attack needs about 36, 500 packets with a success probability 0.5, and the complexity of our attack is equivalent to about 220 computations of the RC4 key setups. Since our attack is passive, it is difficult for both WEP users and administrators to detect our attack.

  9. Substance P induces localization of MIF/α1-inhibitor-3 complexes to umbrella cells via paracellular transit through the urothelium in the rat bladder

    Directory of Open Access Journals (Sweden)

    Vera Pedro L

    2006-09-01

    Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF is released into the intraluminal fluid during bladder inflammation in the rat complexed to α1-inhibitor-3 (A1-I3; a rodent proteinase inhibitor in the α-macroglobulin family. The location of A1-I3 in the bladder had not been investigated. Therefore, we examined the location of A1-I3 and MIF/A1-I3 complexes in the bladder and changes due to experimental inflammation. Methods Anesthetized male rats had bladders removed with no treatment (intact or were injected with Substance P (SP; s.c.; saline vehicle. After one hour intraluminal fluid was removed, bladder was excised and MIF and A1-I3 levels were determined using ELISA and/or western-blotting. MIF co-immunoprecipitation determined MIF/A1-I3 complexes in the bladder. Bladder sections were immunostained for A1-I3 and MIF/A1-I3. Results A1-I3 immunostaining was observed in interstitial spaces throughout the bladder (including submucosa but not urothelium in intact and saline-treated rats. RT-PCR showed that the bladder does not synthesize A1-I3, therefore, A1-I3 in the interstitial space of the bladder must be plasma derived. In SP-treated rats, A1-I3 in the bladder increased and A1-I3 was observed traversing through the urothelium. Umbrella cells that do not show MIF and/or A1-I3 immunostaining in intact or saline-treated rats, showed co-localization of MIF and A1-I3 after SP-treatment. Western blotting demonstrated that in the bladder MIF formed non-covalent interactions and also binds covalently to A1-I3 to form high molecular weight MIF/A1-I3 complexes (170, 130 and 75-kDa, respectively, verified by co-immunoprecipitation. SP-induced inflammation selectively reduced 170-kDa MIF/A1-I3 in the bladder while increasing 170 and 130-kDa MIF/A1-I3 in the intraluminal fluid. Conclusion A1-I3 and MIF/A1-I3 complexes are resident in bladder interstitium. During SP-induced inflammation, MIF/A1-I3 complexes are released from the bladder

  10. Crystallization of a Nonclassical Kazal-type Carcinoscorpius Rotundicauda Serine Protease Inhibitor, CrSPI-1, Complexed with Subtilisin

    Energy Technology Data Exchange (ETDEWEB)

    Tulsidas, S.; Thangamani, S; Ho, B; Sivaraman, J; Ding, J

    2009-01-01

    Serine proteases play a major role in host-pathogen interactions. The innate immune system is known to respond to invading pathogens in a nonspecific manner. The serine protease cascade is an essential component of the innate immune system of the horseshoe crab. The serine protease inhibitor CrSPI isoform 1 (CrSPI-1), a unique nonclassical Kazal-type inhibitor of molecular weight 9.3 kDa, was identified from the hepatopancreas of the horseshoe crab Carcinoscorpius rotundicauda. It potently inhibits subtilisin and constitutes a powerful innate immune defence against invading microbes. Here, the cloning, expression, purification and cocrystallization of CrSPI-1 with subtilisin are reported. The crystals diffracted to 2.6 {angstrom}resolution and belonged to space group P2{sub 1}, with unit-cell parameters a = 73.8, b = 65.0, c = 111.9 {angstrom}, {beta} = 95.4. The Matthews coefficient (VM = 2.64 {angstrom}3 Da-1, corresponding to 53% solvent content) and analysis of the preliminary structure solution indicated the presence of one heterotrimer (1:2 ratio of CrSPI-1:subtilisin) and one free subtilisin molecule in the asymmetric unit.

  11. FLOODING ATTACK AWARE SECURE AODV

    OpenAIRE

    Madhavi, S; K. Duraiswamy

    2013-01-01

    Providing security in a Mobile Ad hoc Network (MANET) is a challenging task due to its inherent nature. Flooding is a type of Denial of Service (DoS) attack in MANET. Intentional flooding may lead to disturbances in the networking operation. This kind of attack consumes battery power, storage space and bandwidth. Flooding the excessive number of packets may degrade the performance of the network. This study considers hello flooding attack. As the hello packets are continuously flooded by the ...

  12. Quinoline-2-carboxaldehyde thiosemicarbazones and their Cu(II) and Ni(II) complexes as topoisomerase IIa inhibitors.

    Science.gov (United States)

    Bisceglie, Franco; Musiari, Anastasia; Pinelli, Silvana; Alinovi, Rossella; Menozzi, Ilaria; Polverini, Eugenia; Tarasconi, Pieralberto; Tavone, Matteo; Pelosi, Giorgio

    2015-11-01

    A series of quinoline-2-carboxaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes were synthesized and characterized. In all complexes the ligands are in the E configuration with respect to the imino bond and behave as terdentate. The copper(II) complexes form square planar derivatives with one molecule of terdentate ligand and chloride ion. A further non-coordinated chloride ion compensates the overall charge. Nickel(II) ions form instead octahedral complexes with two ligands for each metal ion, independently from the stoichiometric metal:ligand ratio used in the synthesis. Ligands and complexes were tested for their antiproliferative properties on histiocytic lymphoma cell line U937. Copper(II) derivatives are systematically more active than the ligands and the nickel complexes. All copper derivatives result in inhibiting topoisomerase IIa in vitro. Computational methods were used to propose a model to explain the different extent of inhibition presented by these compounds. The positive charge of the dissociated form of the copper complexes may play a key role in their action. PMID:26335598

  13. Seven Deadliest Social Network Attacks

    CERN Document Server

    Timm, Carl

    2010-01-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting social networks? Then you need Seven Deadliest Social Network Attacks. This book pinpoints the most dangerous hacks and exploits specific to social networks like Facebook, Twitter, and MySpace, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. Attacks detailed in this book include: Social Networking Infrastruct

  14. Tracing Technique for Blaster Attack

    CERN Document Server

    S., Siti Rahayu; S., Shahrin; A., Faizal M; M, Mohd Zaki; R, Irda

    2009-01-01

    Blaster worm of 2003 is still persistent, the infection appears to have successfully transitioned to new hosts as the original systems are cleaned or shut off, suggesting that the Blaster worm, and other similar worms, will remain significant Internet threats for many years after their initial release. This paper is to propose technique on tracing the Blaster attack from various logs in different OSI layers based on fingerprint of Blaster attack on victim logs, attacker logs and IDS alert log. The researchers intended to do a preliminary investigation upon this particular attack so that it can be used for further research in alert correlation and computer forensic investigation.

  15. The Timing of Terrorist Attacks

    DEFF Research Database (Denmark)

    Jensen, Thomas

    2016-01-01

    I use a simple optimal stopping model to derive policy relevant insights on the timing of one-shot attacks by small autonomous terrorist units or “lone wolf” individuals. A main insight is that an increase in proactive counterterrorism measures can lead to a short term increase in the number...... of attempted terrorist attacks because it makes it more risky for existing terrorist units to pursue further development of capabilities. This is consistent with the events in London in 2005 where a terrorist attack on 7 July was followed by a similar but unsuccessful attack two weeks later....

  16. Seven Deadliest Web Application Attacks

    CERN Document Server

    Shema, Mike

    2010-01-01

    Do you need to keep up with the latest hacks, attacks, and exploits effecting web applications? Then you need Seven Deadliest Web Application Attacks. This book pinpoints the most dangerous hacks and exploits specific to web applications, laying out the anatomy of these attacks including how to make your system more secure. You will discover the best ways to defend against these vicious hacks with step-by-step instruction and learn techniques to make your computer and network impenetrable. .. .. Attacks detailed in this book include: ..: ..; Cross-Site Scripting (XSS) ..; Cross-Site Request Fo

  17. Detonation nanodiamond complexes with cancer stem cells inhibitors or paracrine products of mesenchymal stem cells as new potential medications

    Science.gov (United States)

    Konoplyannikov, A. G.; Alekseenskiy, A. E.; Zlotin, S. G.; Smirnov, B. B.; Kalsina, S. Sh.; Lepehina, L. A.; Semenkova, I. V.; Agaeva, E. V.; Baboyan, S. B.; Rjumshina, E. A.; Nosachenko, V. V.; Konoplyannikov, M. A.

    2015-09-01

    Combined use of complexes of the most active chemotherapeutic drugs and detonation nanodiamonds (DND) is a new trend in cancer therapy, which is probably related to selective chemotherapeutic drug delivery by DND to the zone of so-called cancer stem cells (CSC). Stable DND complexes of 4-5 nm size with salinomycin—a strong CSC inhibitor—have been obtained (as a suspension). It has been demonstrated that a complex administration considerably increases the drug antitumor effect on the transplantable tumor of LLC mice. A similar effect has been observed in CSC models in vivo, obtained by exposure of stem cells of normal mice tissues to a carcinogen 1,2-dimethylhydrazine. It has also been found out, that administration of DND complexes with the conditioned medium from mesenchymal stem cells (MSC) cultures to mice results in a considerable stimulation of stem cell pools in normal mice tissues, which can be used in regenerative medicine.

  18. The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b.

    Directory of Open Access Journals (Sweden)

    Katrin Haupt

    2008-12-01

    Full Text Available The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens, binds human complement regulators Factor H and Factor H related protein 1 (FHR-1 from human serum. Here we identify the secreted protein Sbi (Staphylococcus aureus binder of IgG as a ligand that interacts with Factor H by a-to our knowledge-new type of interaction. Factor H binds to Sbi in combination with C3b or C3d, and forms tripartite SbiratioC3ratioFactor H complexes. Apparently, the type of C3 influences the stability of the complex; surface plasmon resonance studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b or C3. As part of this tripartite complex, Factor H is functionally active and displays complement regulatory activity. Sbi, by recruiting Factor H and C3b, acts as a potent complement inhibitor, and inhibits alternative pathway-mediated lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi is a multifunctional bacterial protein, which binds host complement components Factor H and C3 as well as IgG and beta(2-glycoprotein I and interferes with innate immune recognition.

  19. Role of the Renin-Angiotensin-Aldosterone System and Its Pharmacological Inhibitors in Cardiovascular Diseases: Complex and Critical Issues.

    Science.gov (United States)

    Borghi, Claudio; Rossi, Francesco

    2015-12-01

    Hypertension is one of the major risk factor able to promote development and progression of several cardiovascular diseases, including left ventricular hypertrophy and dysfunction, myocardial infarction, stroke, and congestive heart failure. Also, it is one of the major driven of high cardiovascular risk profile in patients with metabolic complications, including obesity, metabolic syndrome and diabetes, as well as in those with renal disease. Thus, effective control of hypertension is a key factor for any preventing strategy aimed at reducing the burden of hypertension-related cardiovascular diseases in the clinical practice. Among various regulatory and contra-regulatory systems involved in the pathogenesis of cardiovascular and renal diseases, renin-angiotensin system (RAS) plays a major role. However, despite the identification of renin and the availability of various assays for measuring its plasma activity, the specific pathophysiological role of RAS has not yet fully characterized. In the last years, however, several notions on the RAS have been improved by the results of large, randomized clinical trials, performed in different clinical settings and in different populations treated with RAS inhibiting drugs, including angiotensin converting enzyme (ACE) inhibitors and antagonists of the AT1 receptor for angiotensin II (ARBs). These findings suggest that the RAS should be considered to have a central role in the pathogenesis of different cardiovascular diseases, for both therapeutic and preventive purposes, without having to measure its level of activation in each patient. The present document will discuss the most critical issues of the pathogenesis of different cardiovascular diseases with a specific focus on RAS blocking agents, including ACE inhibitors and ARBs, in the light of the most recent evidence supporting the use of these drugs in the clinical management of hypertension and hypertension-related cardiovascular diseases.

  20. DNA cleavage, antimicrobial studies and a DFT-based QSAR study of new antimony(III) complexes as glutathione reductase inhibitor.

    Science.gov (United States)

    Tunç, Turgay; Koç, Yasemin; Açık, Leyla; Karacan, Mehmet Sayım; Karacan, Nurcan

    2015-02-01

    New antimony(III) complexes, [Sb(2-aminopyridine)2Cl3] (1a), [Sb(2-aminopyridine)2Br3] (1b), [Sb(5-methyl-2-aminopyridine)2Cl3] (2a), [Sb(5-methyl-2-aminopyridine)2Br3] (2b), [Sb(2-aminopyrimidine)2Cl3] (3a), [Sb(2-aminopyrimidine)2Br3] (3b), [Sb(4,6-dimethoxy-2-aminopyrimidine)2Cl3] (4a), [Sb(4,6-dimethoxy-2-aminopyrimidine)2Br3] (4b), [Sb(2-amino-1,3,5-triazine)2Cl3] (5a), [Sb(2-amino-1,3,5-triazine)2Br3] (5b), [Sb(2-guanidinobenzimidazole) Cl3] (6a), [Sb(2-guanidinobenzimidazole)Br3] (6b) [Sb(2- benzyl-2-thiopseudeourea)2Cl3] (7a) and [Sb(2- benzyl-2-thiopseudeourea)2Br3] (7b) were synthesized. Their structures were characterized by elemental analysis, molecular conductivity, FT-IR, (1)H NMR, LC-MS techniques. Glutathione reductase inhibitor activity, antimicrobial activity and DNA cleavage studies of the complexes were determined. The geometrical structures of the complexes were optimized by DFT/B3LYP method with LANL2DZ as basis set. Calculation results indicated that the equilibrium geometries of all complexes have square pyramidal shape. About 350 molecular descriptors (constitutional, topological, geometrical, electrostatic and quantum chemical parameters) of the complexes were calculated by DFT/B3LYP/LANL2DZ method with CODESSA software. Calculated molecular parameters were correlated to glutathione reductase inhibitory activity values (pIC50) of all complexes by Best Multi-Linear Regression (BMLR) method. Obtained two-parameter QSAR equation shows that increase in "maximum partial charge for a H atom" and decrease in HOMO-LUMO gap would be favorable for the glutathione reductase inhibitory activity. PMID:25459701

  1. DNA cleavage, antimicrobial studies and a DFT-based QSAR study of new antimony(III) complexes as glutathione reductase inhibitor

    Science.gov (United States)

    Tunç, Turgay; Koç, Yasemin; Açık, Leyla; Karacan, Mehmet Sayım; Karacan, Nurcan

    2015-02-01

    New antimony(III) complexes, [Sb(2-aminopyridine)2Cl3] (1a), [Sb(2-aminopyridine)2Br3] (1b), [Sb(5-methyl-2-aminopyridine)2Cl3] (2a), [Sb(5-methyl-2-aminopyridine)2Br3] (2b), [Sb(2-aminopyrimidine)2Cl3] (3a), [Sb(2-aminopyrimidine)2Br3] (3b), [Sb(4,6-dimethoxy-2-aminopyrimidine)2Cl3] (4a), [Sb(4,6-dimethoxy-2-aminopyrimidine)2Br3] (4b), [Sb(2-amino-1,3,5-triazine)2Cl3] (5a), [Sb(2-amino-1,3,5-triazine)2Br3] (5b), [Sb(2-guanidinobenzimidazole) Cl3] (6a), [Sb(2-guanidinobenzimidazole)Br3] (6b) [Sb(2- benzyl-2-thiopseudeourea)2Cl3] (7a) and [Sb(2- benzyl-2-thiopseudeourea)2Br3] (7b) were synthesized. Their structures were characterized by elemental analysis, molecular conductivity, FT-IR, 1H NMR, LC-MS techniques. Glutathione reductase inhibitor activity, antimicrobial activity and DNA cleavage studies of the complexes were determined. The geometrical structures of the complexes were optimized by DFT/B3LYP method with LANL2DZ as basis set. Calculation results indicated that the equilibrium geometries of all complexes have square pyramidal shape. About 350 molecular descriptors (constitutional, topological, geometrical, electrostatic and quantum chemical parameters) of the complexes were calculated by DFT/B3LYP/LANL2DZ method with CODESSA software. Calculated molecular parameters were correlated to glutathione reductase inhibitory activity values (pIC50) of all complexes by Best Multi-Linear Regression (BMLR) method. Obtained two-parameter QSAR equation shows that increase in "maximum partial charge for a H atom" and decrease in HOMO-LUMO gap would be favorable for the glutathione reductase inhibitory activity.

  2. Antithrombin, an Important Inhibitor in Blood Clots.

    Science.gov (United States)

    Zhu, Ying; Cong, Qing-Wei; Liu, Yue; Wan, Chun-Ling; Yu, Tao; He, Guang; He, Lin; Cai, Lei; Chou, Kuo-Chen

    2016-01-01

    Blood coagulation is healthy and lifesaving because it can stop bleeding. It can, however, be a troublemaker as well, causing serious medical problems including heart attack and stroke. Body has complex blood coagulation cascade to modulate the blood clots. In the environment of plasma, the blood coagulation cascade is regulated by antithrombin, which is deemed one of the most important serine protease inhibitors. It inhibits thrombin; it can inhibit factors IXa and Xa as well. Interestingly, its inhibitory ability will be significantly increased with the existence of heparin. In this minireview paper, we are to summarize the structural features of antithrombin, as well as its heparin binding modes and anti-coagulation mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to find more effective approaches or compounds to modulate the antithrombin. PMID:26411319

  3. Thrombolytic drugs for heart attack

    Science.gov (United States)

    ... attack URL of this page: //medlineplus.gov/ency/article/007488.htm Thrombolytic drugs for heart attack To use the sharing features on this page, ... the management of patients with non-ST-elevation acute coronary syndromes: a report ... myocardial infarction: a report of the American College of Cardiology ...

  4. Improved Linear Attacks on the Chinese Block Cipher Standard

    Institute of Scientific and Technical Information of China (English)

    刘明洁; 陈佳哲

    2014-01-01

    The block cipher used in the Chinese Wireless LAN Standard (WAPI), SMS4, was recently renamed as SM4, and became the block cipher standard issued by the Chinese government. This paper gives a method for finding the linear approximations of SMS4. With this method, 19-round one-dimensional approximations are given, which are used to improve the previous linear cryptanalysis of SMS4. The 19-round approximations hold with bias 2−62.27; we use one of them to leverage a linear attack on 23-round SMS4. Our attack improves the previous 23-round attacks by reducing the time complexity. Furthermore, the data complexity of our attack is further improved by the multidimensional linear approach.

  5. Vasoactivity of rucaparib, a PARP-1 inhibitor, is a complex process that involves myosin light chain kinase, P2 receptors, and PARP itself.

    Directory of Open Access Journals (Sweden)

    Cian M McCrudden

    Full Text Available Therapeutic inhibition of poly(ADP-ribose polymerase (PARP, as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699, induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.

  6. Interaction proteins of invertase and invertase inhibitor in cold-stored potato tubers suggested a protein complex underlying post-translational regulation of invertase.

    Science.gov (United States)

    Lin, Yuan; Liu, Jun; Liu, Xun; Ou, Yongbin; Li, Meng; Zhang, Huiling; Song, Botao; Xie, Conghua

    2013-12-01

    The activity of vacuolar invertase (VI) is vital to potato cold-induced sweetening (CIS). A post-translational regulation of VI activity has been proposed which involves invertase inhibitor (VIH), but the mechanism for the interaction between VI and VIH has not been fully understood. To identify the potential partners of VI and VIH, two cDNA libraries were respectively constructed from CIS-resistant wild potato species Solanum berthaultii and CIS-sensitive potato cultivar AC035-01 for the yeast two-hybrid analysis. The StvacINV1 (one of the potato VIs) and StInvInh2B (one of the potato VIHs), previously identified to be associated with potato CIS, were used as baits to screen the two libraries. Through positive selection and sequencing, 27 potential target proteins of StvacINV1 and eight of StInvInh2B were clarified. The Kunitz-type protein inhibitors were captured by StvacINV1 in both libraries and the interaction between them was confirmed by bimolecular fluorescence complementation assay in tobacco cells, reinforcing a fundamental interaction between VI and VIH. Notably, a sucrose non-fermenting-1-related protein kinase 1 was captured by both the baits, suggesting that a protein complex could be necessary for fine turning of the invertase activity. The target proteins clarified in present research provide a route to elucidate the mechanism by which the VI activity can be subtly modulated.

  7. Structure of the catalytic domain of the Tannerella forsythia matrix metallopeptidase karilysin in complex with a tetrapeptidic inhibitor

    DEFF Research Database (Denmark)

    Guevara, Tibisay; Ksiazek, Miroslaw; Skottrup, Peter Durand;

    2013-01-01

    -binding histidines from the protein scaffold, to an octahedral-minus-one metal-coordination sphere. The tryptophan side chain penetrates the deep partially water-filled specificity pocket of Kly18. Together with previous serendipitous product complexes of Kly18, the present results provide the structural......-micromolar binding affinities. Subsequent refinement revealed that inhibition comparable to that of longer peptides could be achieved using the tetrapeptide SWFP. To analyze its binding, the high-resolution crystal structure of the complex between Kly18 and SWFP was determined and it was found that the peptide binds...

  8. Superposition Attacks on Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Funder, Jakob Løvstad; Nielsen, Jesper Buus;

    2011-01-01

    Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece...... string model. While our protocol is classical, it is sound against a cheating unbounded quantum prover and computational zero-knowledge even if the verifier is allowed a superposition attack. Finally, we consider multiparty computation and show that for the most general type of attack, simulation based...... of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security...

  9. Improving Web Application Firewalls to detect advanced SQL injection attacks

    OpenAIRE

    Makiou, Abdelhamid; Begriche, Youcef; Serhrouchni, Ahmed

    2014-01-01

    International audience; Injections flaws which include SQL injection are the most prevalent security threats affecting Web applications[1]. To mitigate these attacks, Web Application Firewalls (WAFs) apply security rules in order to both inspect HTTP data streams and detect malicious HTTP transactions. Nevertheless, attackers can bypass WAF's rules by using sophisticated SQL injection techniques. In this paper, we introduce a novel approach to dissect the HTTP traffic and inspect complex SQL ...

  10. Biological activities of Zn(II)-S-methyl-cysteine complex as antiradical, inhibitor of acid phosphatase enzyme and in vivo antidepressant effects.

    Science.gov (United States)

    Escudero, Graciela E; Martini, Nancy; Jori, Khalil; Jori, Nadir; Maresca, Nahuel R; Laino, Carlos H; Naso, Luciana G; Williams, Patricia A M; Ferrer, Evelina G

    2016-12-01

    The antidepressant effect of simple Zn(II) salts has been proved in several animal models of depression. In this study, a coordination metal complex of Zn(II) having a sulfur containing ligand is tested as antidepressant for the first time. Forced swimming test method on male Wistar rats shows a decrease in the immobility and an increase in the swimming behavior after treatment with [Zn(S-Met)2] (S-Met=S-methyl-l-cysteine) being more effective and remarkable than ZnCl2. The thiobarbituric acid and the pyranine consumption (hydroxyl and peroxyl radicals, respectively) methods were applied to evaluate the antioxidant activity of S-Met and [Zn(S-Met)2] showing evidence of attenuation of hydroxyl but not peroxyl radicals activities. UV-vis studies on the inhibition of acid phosphatase enzyme (AcP) demonstrated that S-methyl-l-cysteine did not produce any effect but, in contrast, [Zn(S-Met)2] complex behaved as a moderate inhibitor. Finally, bioavailability studies were performed by fluorescence spectroscopy denoting the ability of the albumin to transport the complex.

  11. Binding of the Respiratory Chain Inhibitor Antimycin to theMitochondrial bc1 Complex: A New Crystal Structure Reveals an AlteredIntramolecular Hydrogen-Bonding Pattern

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.

    2005-05-10

    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex.Structure-activity-relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28Angstrom resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alpha-A helix.

  12. The Rebound Attack: Cryptanalysis of Reduced Whirlpool and Grøstl

    DEFF Research Database (Denmark)

    Mendel, Florian; Rechberger, Christian; Schläffer, Martin;

    2009-01-01

    In this work, we propose the rebound attack, a new tool for the cryptanalysis of hash functions. The idea of the rebound attack is to use the available degrees of freedom in a collision attack to efficiently bypass the low probability parts of a differential trail. The rebound attack consists...... of an inbound phase with a match-in-the-middle part to exploit the available degrees of freedom, and a subsequent probabilistic outbound phase. Especially on AES based hash functions, the rebound attack leads to new attacks for a surprisingly high number of rounds. We use the rebound attack to construct...... collisions for 4.5 rounds of the 512-bit hash function Whirlpool with a complexity of 2^120 compression function evaluations and negligible memory requirements. The attack can be extended to a near-collision on 7.5 rounds of the compression function of Whirlpool and 8.5 rounds of the similar hash function...

  13. Mitigation of Malicious Attacks on Networks

    CERN Document Server

    Schneider, Christian M; Andrade, Jose S; Havlin, Shlomo; Herrmann, Hans J; 10.1073/pnas.1009440108

    2011-01-01

    Terrorist attacks on transportation networks have traumatized modern societies. With a single blast, it has become possible to paralyze airline traffic, electric power supply, ground transportation or Internet communication. How and at which cost can one restructure the network such that it will become more robust against a malicious attack? We introduce a unique measure for robustness and use it to devise a method to mitigate economically and efficiently this risk. We demonstrate its efficiency on the European electricity system and on the Internet as well as on complex networks models. We show that with small changes in the network structure (low cost) the robustness of diverse networks can be improved dramatically while their functionality remains unchanged. Our results are useful not only for improving significantly with low cost the robustness of existing infrastructures but also for designing economically robust network systems.

  14. Matrix metalloproteinases during and outside of migraine attacks without aura

    DEFF Research Database (Denmark)

    Ashina, M.; Tvedskov, J.F.; Thiesen, Kerstin Lipka;

    2010-01-01

    Ashina M, Tvedskov JF, Lipka K, Bilello J, Penkowa M & Olesen J. Matrix metalloproteinases during and outside of migraine attacks without aura. Cephalalgia 2009. London. ISSN 0333-1024To test the hypothesis that permeability of the blood-brain barrier (BBB) is altered during migraine attack due...... to enhanced activation of matrix metalloproteinases (MMPs), we investigated MMP-3, MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 in the external jugular vein during and outside of migraine attacks in 21 patients with migraine without aura. In addition, we measured plasma levels of several other...... and interictal plasma levels of MMP-7, -8, -10 and TIMP-2 (P > 0.05). Our data suggest that plasma MMP-9 cannot be used as a biomarker of BBB disruption in migraine without aura. Decreased MMP-3 levels are an interesting and unexpected finding warranting further investigation....

  15. Ternary oxovanadium(IV) complexes of ONO-donor Schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: synthesis, characterization, and biological activities.

    Science.gov (United States)

    Yuan, Caixia; Lu, Liping; Gao, Xiaoli; Wu, Yanbo; Guo, Maolin; Li, Ying; Fu, Xueqi; Zhu, Miaoli

    2009-08-01

    A series of oxovanadium complexes with mixed ligands, a tridentate ONO-donor Schiff base ligand [viz., salicylidene anthranilic acid (SAA)], and a bidentate NN ligand [viz., 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz), or 7-methyldipyrido[3,2-a:2',3'-c]phenazine (dppm)], have been synthesized and characterized by elemental analysis, electrospray ionization mass spectrometry, UV-vis spectroscopy, Fourier transform IR spectroscopy, EPR spectroscopy, and X-ray crystallography. Crystal structures of both complexes, [V(IV)O(SAA)(bpy)].0.25bpy and [V(IV)O(SAA)(phen)].0.33H(2)O, reveal that oxovanadium(IV) is coordinated with one nitrogen and two oxygen atoms from the Schiff base and two nitrogen atoms from the bidentate planar ligands, in a distorted octahedral geometry (VO(3)N(3)). The oxidation state of V(IV) with d(1) configuration was confirmed by EPR spectroscopy. The speciation of VO-SAA-bpy in aqueous solution was investigated by potentiomtreic pH titrations, and the results revealed that the main species are two ternary complexes at a pH range of 7.0-7.4, and one is the isolated crystalline complex. The complexes have been found to be potent inhibitors against human protein tyrosine phosphatase 1B (PTP1B) (IC(50) approximately 30-61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly, the [V(IV)O(SAA)(bpy)] complex selectively inhibits PTP1B over the other two phosphatases (approximate ninefold selectivity against SHP-1 and about twofold selectivity against TCPTP). Kinetics assays suggest that the complexes inhibit PTP1B in a competitive and reversible manner. These suggest that the complexes may be promising candidates as novel antidiabetic agents. PMID:19290551

  16. Assessing Terrorist Motivations for Attacking Critical Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Ackerman, G; Abhayaratne, P; Bale, J; Bhattacharjee, A; Blair, C; Hansell, L; Jayne, A; Kosal, M; Lucas, S; Moran, K; Seroki, L; Vadlamudi, S

    2006-12-04

    Certain types of infrastructure--critical infrastructure (CI)--play vital roles in underpinning our economy, security and way of life. These complex and often interconnected systems have become so ubiquitous and essential to day-to-day life that they are easily taken for granted. Often it is only when the important services provided by such infrastructure are interrupted--when we lose easy access to electricity, health care, telecommunications, transportation or water, for example--that we are conscious of our great dependence on these networks and of the vulnerabilities that stem from such dependence. Unfortunately, it must be assumed that many terrorists are all too aware that CI facilities pose high-value targets that, if successfully attacked, have the potential to dramatically disrupt the normal rhythm of society, cause public fear and intimidation, and generate significant publicity. Indeed, revelations emerging at the time of this writing about Al Qaida's efforts to prepare for possible attacks on major financial facilities in New York, New Jersey, and the District of Columbia remind us just how real and immediate such threats to CI may be. Simply being aware that our nation's critical infrastructure presents terrorists with a plethora of targets, however, does little to mitigate the dangers of CI attacks. In order to prevent and preempt such terrorist acts, better understanding of the threats and vulnerabilities relating to critical infrastructure is required. The Center for Nonproliferation Studies (CNS) presents this document as both a contribution to the understanding of such threats and an initial effort at ''operationalizing'' its findings for use by analysts who work on issues of critical infrastructure protection. Specifically, this study focuses on a subsidiary aspect of CI threat assessment that has thus far remained largely unaddressed by contemporary terrorism research: the motivations and related factors that

  17. Insights into the complex formed by matrix metalloproteinase-2 and alloxan inhibitors: molecular dynamics simulations and free energy calculations.

    Directory of Open Access Journals (Sweden)

    Ilenia Giangreco

    Full Text Available Matrix metalloproteinases (MMP are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S(1' specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S(1' subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC(50 = 7.06 is found for BAM, a compound exhibiting also selectivity (>20 towards MMP-2, as compared to MMP-9, the other member of the gelatinases.

  18. WILD PIG ATTACKS ON HUMANS

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, J.

    2013-04-12

    Attacks on humans by wild pigs (Sus scrofa) have been documented since ancient times. However, studies characterizing these incidents are lacking. In an effort to better understand this phenomenon, information was collected from 412 wild pig attacks on humans. Similar to studies of large predator attacks on humans, data came from a variety of sources. The various attacks compiled occurred in seven zoogeographic realms. Most attacks occurred within the species native range, and specifically in rural areas. The occurrence was highest during the winter months and daylight hours. Most happened under non-hunting circumstances and appeared to be unprovoked. Wounded animals were the chief cause of these attacks in hunting situations. The animals involved were typically solitary, male and large in size. The fate of the wild pigs involved in these attacks varied depending upon the circumstances, however, most escaped uninjured. Most human victims were adult males traveling on foot and alone. The most frequent outcome for these victims was physical contact/mauling. The severity of resulting injuries ranged from minor to fatal. Most of the mauled victims had injuries to only one part of their bodies, with legs/feet being the most frequent body part injured. Injuries were primarily in the form of lacerations and punctures. Fatalities were typically due to blood loss. In some cases, serious infections or toxemia resulted from the injuries. Other species (i.e., pets and livestock) were also accompanying some of the humans during these attacks. The fates of these animals varied from escaping uninjured to being killed. Frequency data on both non-hunting and hunting incidents of wild pig attacks on humans at the Savannah River Site, South Carolina, showed quantitatively that such incidents are rare.

  19. Suicide Attacks on the Rise

    OpenAIRE

    CCS Research Staff

    2008-01-01

    This article was published in Culture and Conflict Review (March 2008), v.2 no.2 "The last six weeks has brought some of the worst violence in Afghanistan since 2001. In 2007, there were more than 230 Improvised Explosive Device (IED) attacks and 145 suicide attacks. Casualty rates were at least 25 percent higher in 2007 than the previous year. In the past 18 months, IED attacks have targeted numerous police and army busses, a group of legislators outside a factory at Baghlan, a five-star ...

  20. Multiculturalism & The Charlie Hebdo Attack

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2016-01-01

    The attack on Charlie Hebdo has by many been linked to multiculturalism. But it is unclear exactly how the connection between multiculturalism and the attack should be understood and whether there indeed is such a connection. The article discusses this by distinguishing between different senses o...... of multiculturalism and different ways in which one might think that there is a link between multiculturalism and the attack. On this basis the resulting claims are discussed as to whether they are in fact plausible, which many of them turn out not to be....

  1. The Cyber-Physical Attacker

    DEFF Research Database (Denmark)

    Vigo, Roberto

    2012-01-01

    The world of Cyber-Physical Systems ranges from industrial to national interest applications. Even though these systems are pervading our everyday life, we are still far from fully understanding their security properties. Devising a suitable attacker model is a crucial element when studying...... the security properties of CPSs, as a system cannot be secured without defining the threats it is subject to. In this work an attacker scenario is presented which addresses the peculiarities of a cyber-physical adversary, and we discuss how this scenario relates to other attacker models popular in the security...

  2. Lifestyle Changes for Heart Attack Prevention

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Can a Heart Attack Be Prevented? Lowering your risk factors for coronary ... This Content: NEXT >> Featured Video What is a heart attack? 05/22/2014 Describes how a heart attack ...

  3. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes.

    Science.gov (United States)

    Hightower, Kendra E; Wang, Ruolan; Deanda, Felix; Johns, Brian A; Weaver, Kurt; Shen, Yingnian; Tomberlin, Ginger H; Carter, H Luke; Broderick, Timothy; Sigethy, Scott; Seki, Takahiro; Kobayashi, Masanori; Underwood, Mark R

    2011-10-01

    The integrase inhibitor (INI) dolutegravir (DTG; S/GSK1349572) has significant activity against HIV-1 isolates with raltegravir (RAL)- and elvitegravir (ELV)-associated resistance mutations. As an initial step in characterizing the different resistance profiles of DTG, RAL, and ELV, we determined the dissociation rates of these INIs with integrase (IN)-DNA complexes containing a broad panel of IN proteins, including IN substitutions corresponding to signature RAL and ELV resistance mutations. DTG dissociates slowly from a wild-type IN-DNA complex at 37°C with an off-rate of 2.7 × 10(-6) s(-1) and a dissociative half-life (t(1/2)) of 71 h, significantly longer than the half-lives for RAL (8.8 h) and ELV (2.7 h). Prolonged binding (t(1/2), at least 5 h) was observed for DTG with IN-DNA complexes containing E92, Y143, Q148, and N155 substitutions. The addition of a second substitution to either Q148 or N155 typically resulted in an increase in the off-rate compared to that with the single substitution. For all of the IN substitutions tested, the off-rate of DTG from IN-DNA complexes was significantly slower (from 5 to 40 times slower) than the off-rate of RAL or ELV. These data are consistent with the potential for DTG to have a higher genetic barrier to resistance, provide evidence that the INI off-rate may be an important component of the mechanism of INI resistance, and suggest that the slow dissociation of DTG may contribute to its distinctive resistance profile. PMID:21807982

  4. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes.

    Science.gov (United States)

    Hightower, Kendra E; Wang, Ruolan; Deanda, Felix; Johns, Brian A; Weaver, Kurt; Shen, Yingnian; Tomberlin, Ginger H; Carter, H Luke; Broderick, Timothy; Sigethy, Scott; Seki, Takahiro; Kobayashi, Masanori; Underwood, Mark R

    2011-10-01

    The integrase inhibitor (INI) dolutegravir (DTG; S/GSK1349572) has significant activity against HIV-1 isolates with raltegravir (RAL)- and elvitegravir (ELV)-associated resistance mutations. As an initial step in characterizing the different resistance profiles of DTG, RAL, and ELV, we determined the dissociation rates of these INIs with integrase (IN)-DNA complexes containing a broad panel of IN proteins, including IN substitutions corresponding to signature RAL and ELV resistance mutations. DTG dissociates slowly from a wild-type IN-DNA complex at 37°C with an off-rate of 2.7 × 10(-6) s(-1) and a dissociative half-life (t(1/2)) of 71 h, significantly longer than the half-lives for RAL (8.8 h) and ELV (2.7 h). Prolonged binding (t(1/2), at least 5 h) was observed for DTG with IN-DNA complexes containing E92, Y143, Q148, and N155 substitutions. The addition of a second substitution to either Q148 or N155 typically resulted in an increase in the off-rate compared to that with the single substitution. For all of the IN substitutions tested, the off-rate of DTG from IN-DNA complexes was significantly slower (from 5 to 40 times slower) than the off-rate of RAL or ELV. These data are consistent with the potential for DTG to have a higher genetic barrier to resistance, provide evidence that the INI off-rate may be an important component of the mechanism of INI resistance, and suggest that the slow dissociation of DTG may contribute to its distinctive resistance profile.

  5. Synthesis and evaluation of the complex-forming ability of hydroxypyranones and hydroxypyridinones with Ni (II) as possible inhibitors for urease enzyme in Helicobacter pylori.

    Science.gov (United States)

    Palizban, Abbasali; Saghaie, Lotfollah

    2016-07-01

    The complex-forming ability of 2-methyl-3-hydroxypyran-4-one (1a), 2-ethyl-3-hydroxypyran-4-one (1b), 1,2-dimethyl-3-hydroxypyridin-4-one (4a) and 1-ethyl-2-methyl-3-hydroxypyridin-4-one (4b) with nickel(Ni(II)) were characterized by infrared, ultraviolet, proton nuclear magnetic resonance spectroscopy and melting point. The mole-ratio of nickel:ligands was analyzed by atomic-absorption-spectrometry. The partition-coefficients (KOW) of the compounds were also determined. The binding of ligands with Ni(II) are through deprotonated hydroxyl group (-O(-), disapeared at 3259 cm(-1)) and ioan-pairs of carbonyl group (=CO(.), shifted from 1650 to 1510-1515 cm(-1)). The characterization of complex geometry for bis-(2-methyl-3-hydroxypyranonato)Ni(II) (5a) and bis-(2-ethyl-3-hydroxypyranonato)Ni(II) (5b) predicted to be square-planer while for bis-(1,2-dimethyl-3-hydroxypyridinonato)Ni(II) (5c) and bis-(1-ethyl-2-methyl-3-hydroxypyridinonato)Ni(II) (5d) distorted to tetrahedral-geometry. Inhibitors of Helicobacter pylori urease are nickel chelators. The compounds 1a, 4a and 4b are likely suitable ligands with complex forming-ability to make complexes of 5a, 5c and 5d with nickel. The KOW values show the compound 5c with low partition-coefficient is more suitable ligand with lower penetration from GI lumen. Future studies demand to find out the biological activity of developed compounds on H. pylori. PMID:27651814

  6. Synthesis and evaluation of the complex-forming ability of hydroxypyranones and hydroxypyridinones with Ni (II as possible inhibitors for urease enzyme in Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Abbasali Palizban

    2016-01-01

    Full Text Available The complex-forming ability of 2-methyl-3-hydroxypyran-4-one ( 1a , 2-ethyl-3-hydroxypyran-4-one ( 1b , 1,2-dimethyl-3-hydroxypyridin-4-one ( 4a and 1-ethyl-2-methyl-3- hydroxypyridin-4-one ( 4b with nickel(Ni(II were characterized by infrared, ultraviolet, proton nuclear magnetic resonance spectroscopy and melting point. The mole-ratio of nickel:ligands was analyzed by atomic-absorption-spectrometry. The partition-coefficients (K OW of the compounds were also determined. The binding of ligands with Ni(II are through deprotonated hydroxyl group (-O - , disapeared at 3259 cm -1 and ioan-pairs of carbonyl group (=CO . , shifted from 1650 to 1510-1515 cm -1 . The characterization of complex geometry for bis-(2-methyl-3-hydroxypyranonatoNi(II ( 5a and bis-(2-ethyl-3-hydroxypyranonatoNi(II ( 5b predicted to be square-planer while for bis-(1,2-dimethyl-3-hydroxypyridinonatoNi(II ( 5c and bis-(1-ethyl-2-methyl-3-hydroxypyridinonatoNi(II ( 5d distorted to tetrahedral-geometry. Inhibitors of Helicobacter pylori urease are nickel chelators. The compounds 1a , 4a and 4b are likely suitable ligands with complex forming-ability to make complexes of 5a , 5c and 5d with nickel. The K OW values show the compound 5c with low partition-coefficient is more suitable ligand with lower penetration from GI lumen. Future studies demand to find out the biological activity of developed compounds on H. pylori.

  7. Synthesis and evaluation of the complex-forming ability of hydroxypyranones and hydroxypyridinones with Ni (II) as possible inhibitors for urease enzyme in Helicobacter pylori

    Science.gov (United States)

    Palizban, Abbasali; Saghaie, Lotfollah

    2016-01-01

    The complex-forming ability of 2-methyl-3-hydroxypyran-4-one (1a), 2-ethyl-3-hydroxypyran-4-one (1b), 1,2-dimethyl-3-hydroxypyridin-4-one (4a) and 1-ethyl-2-methyl-3-hydroxypyridin-4-one (4b) with nickel(Ni(II)) were characterized by infrared, ultraviolet, proton nuclear magnetic resonance spectroscopy and melting point. The mole-ratio of nickel:ligands was analyzed by atomic-absorption-spectrometry. The partition-coefficients (KOW) of the compounds were also determined. The binding of ligands with Ni(II) are through deprotonated hydroxyl group (-O-, disapeared at 3259 cm-1) and ioan-pairs of carbonyl group (=CO., shifted from 1650 to 1510-1515 cm-1). The characterization of complex geometry for bis-(2-methyl-3-hydroxypyranonato)Ni(II) (5a) and bis-(2-ethyl-3-hydroxypyranonato)Ni(II) (5b) predicted to be square-planer while for bis-(1,2-dimethyl-3-hydroxypyridinonato)Ni(II) (5c) and bis-(1-ethyl-2-methyl-3-hydroxypyridinonato)Ni(II) (5d) distorted to tetrahedral-geometry. Inhibitors of Helicobacter pylori urease are nickel chelators. The compounds 1a, 4a and 4b are likely suitable ligands with complex forming-ability to make complexes of 5a, 5c and 5d with nickel. The KOW values show the compound 5c with low partition-coefficient is more suitable ligand with lower penetration from GI lumen. Future studies demand to find out the biological activity of developed compounds on H. pylori. PMID:27651814

  8. The accountability problem of flooding attacks in service-oriented architectures

    DEFF Research Database (Denmark)

    Jensen, Meiko; Schwenk, Jörg

    2009-01-01

    The threat of Denial of Service attacks poses a serious problem to the security of network-based services in general. For flooding attacks against service-oriented applications, this threat is dramatically amplified with potentially much higher impact and very little effort on the attacker's side....... Additionally, due to the high distribution of a SOA application's components, fending such attacks becomes a far more complex task. In this paper, we present the problem of accountability, referring to the issue of resolving the attacker in a highly distributed service-oriented application. Using a general...

  9. Social Engineering:A Partial Technical attack

    OpenAIRE

    P.S.Maan; Manish Sharma

    2012-01-01

    This paper suggests the crystal clear concept behind the social engineering attack. Basically social engineering is a non technical attack. But social engineering attack is an attack on human psychology to get the information, but using what? Basically it is an attack on human psychology by using some technical skills or technology. Social engineering attack has many types like fake mail, telephonic cheat etc. which are impossible without any technical skills, so in this paper we suggest that...

  10. Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Fujino, Aiko; Fukushima, Kei; Kubota, Takaharu; Kosugi, Tomomi; Takimoto-Kamimura, Midori, E-mail: m.kamimura@teijin.co.jp [Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo 191-8512 (Japan)

    2013-11-01

    The Gly-rich loop of cyclin-dependent kinase 2 (CDK2) bound to TEI-I01800 as an MK2 specific inhibitor forms a β-sheet which is a common structure in CDK2–ligand complexes. Here, the reason why TEI-I01800 does not become a strong inhibitor against CDK2 based on the conformation of TEI-I01800 is presented. Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the MK2–TEI-I01800 complex has been reported; its Gly-rich loop was found to form an α-helix, not a β-sheet as has been observed for other Ser/Thr kinases. TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 Å resolution. Interestingly, the Gly-rich loop of CDK2 formed a β-sheet that was different from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly-rich loop from a β-sheet to an α-helix by collision between Leu70 and a p-ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. In summary, the results of this study suggest that the reason for the selectivity of TEI-I01800 is the favourable conformation of TEI-I01800 itself, making it suitable for binding to the α-form MK2.

  11. Positive Mode LC-MS/MS Analysis of Chondroitin Sulfate Modified Glycopeptides Derived from Light and Heavy Chains of The Human Inter-α-Trypsin Inhibitor Complex.

    Science.gov (United States)

    Gomez Toledo, Alejandro; Nilsson, Jonas; Noborn, Fredrik; Sihlbom, Carina; Larson, Göran

    2015-12-01

    The inter-α-trypsin inhibitor complex is a macromolecular arrangement of structurally related heavy chain proteins covalently cross-linked to the chondroitin sulfate (CS) chain of the proteoglycan bikunin. The inter-α-trypsin inhibitor complex is abundant in plasma and associated with inflammation, kidney diseases, cancer and diabetes. Bikunin is modified at Ser-10 by a single low-sulfated CS chain of 23-55 monosaccharides with 4-9 sulfate groups. The innermost four monosaccharides (GlcAβ3Galβ3Galβ4Xylβ-O-) compose the linkage region, believed to be uniform with a 4-O-sulfation to the outer Gal. The cross-linkage region of the bikunin CS chain is located in the nonsulfated nonreducing end, (GalNAcβ4GlcAβ3)(n), to which heavy chains (H1-H3) may be bound in GalNAc to Asp ester linkages. In this study we employed a glycoproteomics protocol to enrich and analyze light and heavy chain linkage and cross-linkage region CS glycopeptides derived from the IαI complex of human plasma, urine and cerebrospinal fluid samples. The samples were trypsinized, enriched by strong anion exchange chromatography, partially depolymerized with chondroitinase ABC and analyzed by LC-MS/MS using higher-energy collisional dissociation. The analyses demonstrated that the CS linkage region of bikunin is highly heterogeneous. In addition to sulfation of the Gal residue, Xyl phosphorylation was observed although exclusively in urinary samples. We also identified novel Neu5Ac and Fuc modifications of the linkage region as well as the presence of mono- and disialylated core 1 O-linked glycans on Thr-17. Heavy chains H1 and H2 were identified cross-linked to GalNAc residues one or two GlcA residues apart and H1 was found linked to either the terminal or subterminal GalNAc residues. The fragmentation behavior of CS glycopeptides under variable higher-energy collisional dissociation conditions displays an energy dependence that may be used to obtain complementary structural details. Finally

  12. Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity

    International Nuclear Information System (INIS)

    The Gly-rich loop of cyclin-dependent kinase 2 (CDK2) bound to TEI-I01800 as an MK2 specific inhibitor forms a β-sheet which is a common structure in CDK2–ligand complexes. Here, the reason why TEI-I01800 does not become a strong inhibitor against CDK2 based on the conformation of TEI-I01800 is presented. Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the MK2–TEI-I01800 complex has been reported; its Gly-rich loop was found to form an α-helix, not a β-sheet as has been observed for other Ser/Thr kinases. TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 Å resolution. Interestingly, the Gly-rich loop of CDK2 formed a β-sheet that was different from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly-rich loop from a β-sheet to an α-helix by collision between Leu70 and a p-ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. In summary, the results of this study suggest that the reason for the selectivity of TEI-I01800 is the favourable conformation of TEI-I01800 itself, making it suitable for binding to the α-form MK2

  13. The Attack Navigator

    NARCIS (Netherlands)

    Probst, Christian W.; Willemson, Jan; Pieters, Wolter; Mauw, Sjouke; Kordy, Barbara; Jajodia, Sushil

    2016-01-01

    The need to assess security and take protection decisions is at least as old as our civilisation. However, the complexity and develop-ment speed of our interconnected technical systems have surpassed our capacity to imagine and evaluate risk scenarios. This holds in particular for risks that are cau

  14. Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as Hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex

    Energy Technology Data Exchange (ETDEWEB)

    Arasappan, Ashok; Njoroge, F. George; Parekh, Tejal N.; Yang, Xiaozheng; Pichardo, John; Butkiewicz, Nancy; Prongay, Andrew; Yao, Nanhua; Girijavallabhan, Viyyoor (SPRI)

    2008-06-30

    Synthesis and HCV NS3 serine protease inhibitory activity of some novel 2-oxoimidazolidine-4-carboxylic acid derivatives are reported. Inhibitors derived from this new P2 core exhibited activity in the low {micro}M range. X-ray structure of an inhibitor, 15c bound to the protease is presented.

  15. Social Engineering:A Partial Technical attack

    Directory of Open Access Journals (Sweden)

    P. S. Maan

    2012-03-01

    Full Text Available This paper suggests the crystal clear concept behind the social engineering attack. Basically social engineering is a non technical attack. But social engineering attack is an attack on human psychology to get the information, but using what? Basically it is an attack on human psychology by using some technical skills or technology. Social engineering attack has many types like fake mail, telephonic cheat etc. which are impossible without any technical skills, so in this paper we suggest that , it is a partial technical attack and can be divided in human based and typical computer based social engineering attack.

  16. An Enhanced SYN Cookie Defence Method for TCP DDoS Attack

    Directory of Open Access Journals (Sweden)

    Bo Hang

    2011-08-01

    Full Text Available With the development of network, the issues of network security are rapidly becoming a serious problem, and the Denial of Service (DoS attack has already become the greatest threat to the network. SYN Flood attack is one of the most common distributed denial of service attack way (DDoS. This paper presents an improved SYN Cookie method, designing a novel attack detector processing and a enhanced attack respondor with a new cookie verification algorithm and changing the definition of cookie field, to reduce algorithm complexity with the ensurance of security. The experiment results show that the proposed method provided an average computational complexity reduction of 30% compared with the traditional method. The new method can be an effective defense against the TCP SYN Flood attack with a lower complexity.

  17. Microarchitectural Side-Channel Attacks

    OpenAIRE

    Gallais, Jean-Francois

    2013-01-01

    Cryptanalysis is the science which evaluates the security of a cryptosystem and detects its weaknesses and flaws. Initially confined to the black-box model, where only the input and output data were considered, cryptanalysis is now broadened to the security evaluation of the physical implementation of a cryptosystem. The implementation attacks which compose physical cryptanalysis are divided into fault attacks, exploiting the effect of disruption of the normal functioning of the device, and s...

  18. Acute ischemic cerebral attack

    Directory of Open Access Journals (Sweden)

    Franco-Garcia Samir

    2010-12-01

    Full Text Available The decrease of the cerebral blood flow below the threshold of autoregulation led to changes of cerebral ischemia and necrosis that traduce in signs and symtoms of focal neurologic dysfunction called acute cerebrovascular symdrome (ACS or stroke. Two big groups according to its etiology are included in this category the hemorragic that constitue a 20% and the ischemic a 80% of cases. Great interest has wom the ischemic ACS because of its high social burden, being the third cause of no violent death in the world and the first of disability. Many risk factors favor the presentation of these events and some of them are susceptible of modification and therfore are objetives of primary prevention just as the control of diabetes, hypertension and the practice of healthy habits of life. The advances in the knowledge of the physiopatology, had taken to sustantial change in the nomenclature and management of ischemic ACS. Within these changes it was substituted the term cerebrovascular accident fo acute stroke, making emphasis in the key rol of a timely management with goals of time similiar to the acute coronary syndrome. It was redefined the time of acute ischemic attack to a one hour. Once stablished the cerebrovascular attack the semiology of symtoms with frecuency will led us make a topographic diagnosis of the in injury that joined to the cerebral TAC will allow us to exclude an hemorragic event and to start the treatment. In the management of these patients its essential the coordination of the differents teams of work, from the early recognition of symtoms on the part of patients andthe family, the rapid activation and response of emergency systems and the gearing of health care institutions. Are pillars of treatment: the abcde of reanimatiion, to avoid the hiperpirexis, the seizures, the hipoglicemy, the hiperglicemy, to achieve the thrombolysis in the first three hours of the begining of symtoms, to use antiplatelets, antithrombotic profilaxis

  19. A heterotetrameric alpha-amylase inhibitor from emmer (Triticum dicoccon Schrank) seeds.

    Science.gov (United States)

    Capocchi, A; Muccilli, V; Cunsolo, V; Saletti, R; Foti, S; Fontanini, D

    2013-04-01

    Plants have developed a constitutive defense system against pest attacks, which involves the expression of a set of inhibitors acting on heterologous amylases of different origins. Investigating the soluble protein complement of the hulled wheat emmer we have isolated and characterized a heterotetrameric α-amylase inhibitor (ETI). Based on mass spectrometry data, it is an assembly of proteins highly similar to the CM2/CM3/CM16 found in durum wheat. Our data indicate that these proteins can also inhibit exogenous α-amylases in binary assemblies. The calculated dissociation constants (K(i)) for the pancreatic porcine amylase- and human salivary amylase-ETI complexes are similar to those found in durum and soft wheat. Homology modeling of the CM subunits indicate structural similarities with other proteins belonging to the cereal family of trypsin/α-amylase inhibitors; a possible homology modeled structure for a tetrameric assembly of the subunits is proposed. PMID:23320956

  20. Interactions between Barley a-Amylases, Substrates, Inhibitors and Regulatory Proteins

    DEFF Research Database (Denmark)

    Hachem, Maher Abou; Bozonnet, Sophie; Willemoës, Martin;

    2006-01-01

    Barley a-amylase binds sugars at two sites on the enzyme surface in addition to the active site. Crystallography and site-directed mutagenesis highlight the importance of aromatic residues at these surface sites as demonstrated by Kd values determined for ß-cyclodextrin by surface plasmon resonance...... by mutagenesis, crystallography and microcalorimetry. Further improvement of recombinant AMY2 production allows future direct mutational analysis in this isozyme. Specific proteinaceous inhibitors act on a-amylases of different origin. In the complex of barley a-amylase/subtilisin inhibitor (BASI) with AMY2...... of the disulphide reductase thioredoxin h that attacks a specific disulphide bond in BASI and, remarkably, reduces two different disulphide bonds in the barley monomeric and dimeric amylase inhibitors that both belong to the CM-proteins and inhibit animal a-amylase....

  1. Several Novel N-Donor Tridentate Ligands Formed in Chemical Studies of New fac-Re(CO)3 Complexes Relevant to fac-99mTc(CO)3 Radiopharmaceuticals. Attack of a Terminal Amine on Coordinated Acetonitrile

    OpenAIRE

    Perera, Theshini; Marzilli, Patricia A.; Fronczek, Frank R.; Marzilli, Luigi G.

    2010-01-01

    A novel ligand was discovered in which acetonitrile appears to have inserted between the two protons and the nitrogen of a primary amine. A proposed pathway for this process involves a putative seven-membered chelate ring (formed by attack of a primary amine on coordinated acetonitrile) that undergoes proton transfer and rearrangement. The pathway is supported by the structure of a related compound that has a methyl group in place of one of the protons.

  2. Impossible Differential Attacks on 13-Round CLEFIA-128

    Institute of Scientific and Technical Information of China (English)

    Hamid Mala; Mohammad Dakhilalian; Mohsen Shakiba

    2011-01-01

    CLEFIA,a new 128-bit block cipher proposed by Sony Corporation,is increasingly attracting cryptanalysts'attention.In this paper,we present two new impossible differential attacks on 13 rounds of CLEFIA-128.The proposed attacks utilize a variety of previously known techniques,in particular the hash table technique and redundancy in the key schedule of this block cipher.The first attack does not consider the whitening layers of CLEFIA,requires 2109.5 chosen plaintexts,and has a running time equivalent to about 2112.9 encryptions.The second attack preserves the whitening layers,requires 2117.8 chosen plaintexts,and has a total time complexity equivalent to about 2121.2 encryptions.

  3. Attack Coverage in High-Level Men's Volleyball: Organization on the Edge of Chaos?

    Science.gov (United States)

    Laporta, Lorenzo; Nikolaidis, Pantelis; Thomas, Luke; Afonso, José

    2015-09-29

    Change is pervasive, but emerging patterns are occasionally detectable through analysis of systemic behaviors. Match analysis uses these patterns in order to reduce the degree of improvisation and to optimize the training process. However, it is possible that certain game phases elude systematic patterning. In this vein, our aim was to analyze the case of attack coverage in men's volleyball, as we suspected it would elude systematic patterning and has received negligible attention in scientific research. We analyzed the occurrence of attack coverage in 4544 plays of the 2011 Volleyball World League. A Chi-square test with residual adjusted values was applied to explore significant associations between variables. A Monte Carlo correction was applied, as some cells had n<5. Effect sizes were determined using Cramer's V. Overall, attack coverage occurred in 3.89% of ball possessions, and 23 distinct structures emerged. These structures lacked significant associations with the game complex, setting zone, and effect of attack coverage. Conversely, attack coverage structures showed significant associations with the attack zone and tempo, with very strong effect sizes (V=0.472 and V=0.521, respectively). As certain attack zones are deeply associated with attack tempo, it is apparent that quicker attack plays affect attack coverage structuring, promoting the formation of less complex structures. Ultimately, attack coverage structures seem to depend on momentary constraints, thereby rendering rigid systematization impracticable. Still, we contended that a principle-based approach might be suitable. This invites researchers to rethink how to interpret game regularities. PMID:26557208

  4. A cluster based approach for wormhole attack detection in wireless sensor networks

    Directory of Open Access Journals (Sweden)

    Maliheh Shahryari

    2015-02-01

    Full Text Available Due to the need of cooperation among nodes to relay packets, wireless sensor networks are very vulnerable to attacks in all layers of the network. One of these severe attacks is the wormhole attack. Detection of wormhole attack is hard, because it can be easily implemented by attacker without having knowledge of nodes in the network or it can be compromised by any legal node in the network. To date, the most of proposed protocols to defend against wormhole attacks are made by adopting synchronized clocks, directional antennas or strong assumptions in order to detect wormhole attacks. A method based on clustering is presented in this paper to detect this type of attacks. This method is implemented in static and mobile networks. The superiority of our protocol is that during the attack prevention or attack detection, the malicious nodes are detected and requires no additional hardware or complex calculations. Simulation results are perused with the NS-2 simulator and the protocol has been evaluated in terms of packet drop ratio, throughput, delay and energy consumption compared to a network without or under attack. Simulation results show that our protocol is practical and effective in improving resilience against wormhole attacks.

  5. Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to pCDK2-cyclin A complex.

    Science.gov (United States)

    Kosmopoulou, Magda N; Leonidas, Demetres D; Chrysina, Evangelia D; Bischler, Nicolas; Eisenbrand, Gerhard; Sakarellos, Constantinos E; Pauptit, Richard; Oikonomakos, Nikos G

    2004-06-01

    The binding of indirubin-5-sulphonate (E226), a potential anti-tumour agent and a potent inhibitor (IC(50) = 35 nm) of cyclin-dependent kinase 2 (CDK2) and glycogen phosphorylase (GP) has been studied by kinetic and crystallographic methods. Kinetic analysis revealed that E226 is a moderate inhibitor of GPb (K(i) = 13.8 +/- 0.2 micro m) and GPa (K(i) = 57.8 +/- 7.1 micro m) and acts synergistically with glucose. To explore the molecular basis of E226 binding we have determined the crystal structure of the GPb/E226 complex at 2.3 A resolution. Structure analysis shows clearly that E226 binds at the purine inhibitor site, where caffeine and flavopiridol also bind [Oikonomakos, N.G., Schnier, J.B., Zographos, S.E., Skamnaki, V.T., Tsitsanou, K.E. & Johnson, L.N. (2000) J. Biol. Chem.275, 34566-34573], by intercalating between the two aromatic rings of Phe285 and Tyr613. The mode of binding of E226 to GPb is similar, but not identical, to that of caffeine and flavopiridol. Comparative structural analyses of the GPb-E226, GPb-caffeine and GPb-flavopiridol complex structures reveal the structural basis of the differences in the potencies of the three inhibitors and indicate binding residues in the inhibitor site that can be exploited to obtain more potent inhibitors. Structural comparison of the GPb-E226 complex structure with the active pCDK2-cyclin A-E226 complex structure clearly shows the different binding modes of the ligand to GPb and CDK2; the more extensive interactions of E226 with the active site of CDK2 may explain its higher affinity towards the latter enzyme. PMID:15153119

  6. X-ray structure of the ternary MTX·NADPH complex of the anthrax dihydrofolate reductase: A pharmacophore for dual-site inhibitor design

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Brad C.; Wan, Qun; Ahmad, Md Faiz; Langan, Paul; Dealwis, Chris G.; (Case Western); (LANL)

    2009-11-18

    For reasons of bioterrorism and drug resistance, it is imperative to identify and develop new molecular points of intervention against anthrax. Dihydrofolate reductase (DHFR) is a highly conserved enzyme and an established target in a number of species for a variety of chemotherapeutic programs. Recently, the crystal structure of B. anthracis DHFR (baDHFR) in complex with methotrexate (MTX) was determined and, based on the structure, proposals were made for drug design strategies directed against the substrate binding site. However, little is gleaned about the binding site for NADPH, the cofactor responsible for hydride transfer in the catalytic mechanism. In the present study, X-ray crystallography at 100 K was used to determine the structure of baDHFR in complex with MTX and NADPH. Although the NADPH binding mode is nearly identical to that seen in other DHFR ternary complex structures, the adenine moiety adopts an off-plane tilt of nearly 90 deg. and this orientation is stabilized by hydrogen bonds to functionally conserved Arg residues. A comparison of the binding site, focusing on this region, between baDHFR and the human enzyme is discussed, with an aim at designing species-selective therapeutics. Indeed, the ternary model, refined to 2.3{angstrom} resolution, provides an accurate template for testing the feasibility of identifying dual-site inhibitors, compounds that target both the substrate and cofactor binding site. With the ternary model in hand, using in silico methods, several compounds were identified which could potentially form key bonding contacts in the substrate and cofactor binding sites. Ultimately, two structurally distinct compounds were verified that inhibit baDHFR at low {mu}M concentrations. The apparent K{sub d} for one of these, (2-(3-(2-(hydroxyimino)-2-(pyridine-4-yl)-6,7-dimethylquinoxalin-2-yl)-1-(pyridine-4-yl)ethanone oxime), was measured by fluorescence spectroscopy to be 5.3 {mu}M.

  7. A binuclear complex constituted by diethyldithiocarbamate and copper(I) functions as a proteasome activity inhibitor in pancreatic cancer cultures and xenografts.

    Science.gov (United States)

    Han, Jinbin; Liu, Luming; Yue, Xiaoqiang; Chang, Jinjia; Shi, Weidong; Hua, Yongqiang

    2013-12-15

    It is a therapeutic strategy for cancers including pancreatic to inhibit proteasome activity. Disulfiram (DSF) may bind copper (Cu) to form a DSF-Cu complex. DSF-Cu is capable of inducing apoptosis in cancer cells by inhibiting proteasome activity. DSF is rapidly converted to diethyldithiocarbamate (DDTC) within bodies. Copper(II) absorbed by bodies is reduced to copper(I) when it enters cells. We found that DDTC and copper(I) could form a binuclear complex which might be entitled DDTC-Cu(I), and it had been synthesized by us in the laboratory. This study is to investigate the anticancer potential of this complex on pancreatic cancer and the possible mechanism. Pancreatic cancer cell lines, SW1990, PANC-1 and BXPC-3 were used for in vitro assays. Female athymic nude mice grown SW1990 xenografts were used as animal models. Cell counting kit-8 (cck-8) assay and flow cytometry were used for analyzing apoptosis in cells. A 20S proteasome assay kit was used in proteasome activity analysis. Western blot (WB) and immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used in tumor sample analysis. The results suggest that DDTC-Cu(I) inhibit pancreatic cancer cell proliferation and proteasome activity in vitro and in vivo. Accumulation of ubiquitinated proteins, and increased p27 as well as decreased NF-κB expression were detected in tumor tissues of DDTC-Cu(I)-treated group. Our data indicates that DDTC-Cu(I) is an effective proteasome activity inhibitor with the potential to be explored as a drug for pancreatic cancer.

  8. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Melendez DP

    2015-08-01

    Full Text Available Dante P Melendez,1,2 Raymund R Razonable1,2 1Division of Infectious Diseases, 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA Abstract: Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246 is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies. Keywords: cytomegalovirus, letermovir, AIC246, terminase, antivirals, transplantation 

  9. Inhibition of Human Steroid 5-Reductase (AKR1D1) by Finasteride and Structure of the Enzyme-Inhibitor Complex

    Energy Technology Data Exchange (ETDEWEB)

    Drury, J.; Di Costanzo, L; Penning, T; Christianson, D

    2009-01-01

    The {Delta}{sup 4}-3-ketosteroid functionality is present in nearly all steroid hormones apart from estrogens. The first step in functionalization of the A-ring is mediated in humans by steroid 5{alpha}- or 5{beta}-reductase. Finasteride is a mechanism-based inactivator of 5{alpha}-reductase type 2 with subnanomolar affinity and is widely used as a therapeutic for the treatment of benign prostatic hyperplasia. It is also used for androgen deprivation in hormone-dependent prostate carcinoma, and it has been examined as a chemopreventive agent in prostate cancer. The effect of finasteride on steroid 5{beta}-reductase (AKR1D1) has not been previously reported. We show that finasteride competitively inhibits AKR1D1 with low micromolar affinity but does not act as a mechanism-based inactivator. The structure of the AKR1D1 {center_dot} NADP{sup +} {center_dot} finasteride complex determined at 1.7 {angstrom} resolution shows that it is not possible for NADPH to reduce the {Delta}{sup 1-2}-ene of finasteride because the cofactor and steroid are not proximal to each other. The C3-ketone of finasteride accepts hydrogen bonds from the catalytic residues Tyr-58 and Glu-120 in the active site of AKR1D1, providing an explanation for the competitive inhibition observed. This is the first reported structure of finasteride bound to an enzyme involved in steroid hormone metabolism.

  10. Angioedema Related to Angiotensin-Converting Enzyme Inhibitors

    OpenAIRE

    Javaud, Nicolas; Achamlal, Jallal; Reuter, Paul-George; Lapostolle, Frédéric; Lekouara, Akim; Youssef, Mustapha; Hamza, Lilia; Karami, Ahmed; Adnet, Frédéric; Fain, Olivier

    2015-01-01

    Abstract The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack. A prospective, multicenter, observational study (...

  11. Complexity

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    The term complexity derives etymologically from the Latin plexus, which means interwoven. Intuitively, this implies that something complex is composed by elements that are difficult to separate. This difficulty arises from the relevant interactions that take place between components. This lack of separability is at odds with the classical scientific method - which has been used since the times of Galileo, Newton, Descartes, and Laplace - and has also influenced philosophy and engineering. In recent decades, the scientific study of complexity and complex systems has proposed a paradigm shift in science and philosophy, proposing novel methods that take into account relevant interactions.

  12. Inhibition of localized attack on the aluminium alloy AA 6351 in glycol/water solutions

    Energy Technology Data Exchange (ETDEWEB)

    Monticelli, C.; Brunoro, G.; Zucchi, F.; Fagioli, F.

    1989-06-01

    The objective of this work was to examine the feasibility of enhancing pitting resistance of AA 6351 (nominal composition: 1% Si, 0.6% Mg, 0.3% Mn, balance Al) by adding suitable inhibitors to the solutions. The compounds used were two inorganic salts: sodium molybdate and sodium tungstate and two derivatives of pyrimidine: 2-aminopyrimidine (2AP) and 2-hydroxypyrimidine (2HP). The inhibiting efficiencies of these substances were tested by both short-time electrochemical tests (galvanic coupling tests and polarization curves) and long-time immersions under experimental conditions causing the localized attack. Molybdate, tungstate and, to some extent, also 2AP efficiently inhibit AA 6351 localized corrosion in degraded solutions at 80/sup 0/C and in pure boiling solutions, for long exposure periods. The short-time electrochemical tests suggest that molybdate and tungstate are able to retard the electrochemical processes occurring on both the aluminium alloy and the small copper cathodic area produced by copper deposition. On the other hand, the 2AP efficiency is attributed to some complexing capability of this pyrimidine derivative towards dissolved copper ions, that are stabilized in solution. 2HP does not prevent AA 6351 localized attack. (orig./MM).

  13. Analytical Characterization of Internet Security Attacks

    Science.gov (United States)

    Sellke, Sarah H.

    2010-01-01

    Internet security attacks have drawn significant attention due to their enormously adverse impact. These attacks includes Malware (Viruses, Worms, Trojan Horse), Denial of Service, Packet Sniffer, and Password Attacks. There is an increasing need to provide adequate defense mechanisms against these attacks. My thesis proposal deals with analytical…

  14. RESIST SRP AGAINST WORMHOLE ATTACK

    Directory of Open Access Journals (Sweden)

    Marjan Kuchaki Rafsanjani

    2013-06-01

    Full Text Available Ad-hoc networks refer to temporary or interim networks which form for special purposes. Actually they are wireless networks with mobile nodes. These networks use no network assisting element for path routing and in these networks available nodes are responsible for path routing. Therefore when malicious nodes want to find a way to interfere with the path routing then the existence of a secure route protocol (SRP can prevent the interference. SRP protocol is one of the secure algorithms of path routing protocol but it is notresistant against wormhole attack. Wormhole attack is considered as a subtle attack in which two malicious nodes make a short connection in network's topology through private or implicit connection and represent two non neighbor nodes as neighbors and prevent the correctoperation of path routing protocol by using this method. One of the methods of preventing wormhole attack is by using packet leashes. We try to decrease the wormhole attack occurrence in this routing protocol by a kind of packet leashes called temporal leashes. We alsowill minimize problems resulting from using temporal leashes by different methods and modifications in its structure.

  15. How to Deal with Weak Interactions in Noncovalent Complexes Analyzed by Electrospray Mass Spectrometry: Cyclopeptidic Inhibitors of the Nuclear Receptor Coactivator 1-STAT6

    OpenAIRE

    Touboul, D.; Maillard, L.; Grässlin, A; Moumne, R; Seitz, M; Robinson, J. A.; R. Zenobi

    2009-01-01

    Mass spectrometry, and especially electrospray ionization, is now an efficient tool to study noncovalent interactions between proteins and inhibitors. It is used here to study the interaction of some weak inhibitors with the NCoA-1/STAT6 protein with KD values in the μM range. High signal intensities corresponding to some nonspecific electrostatic interactions between NCoA-1 and the oppositely charged inhibitors were observed by nanoelectrospray mass spectrometry, due to the use of high ligan...

  16. A peptide derived from the parasite receptor, complement C2 receptor inhibitor trispanning, suppresses immune complex-mediated inflammation in mice.

    Science.gov (United States)

    Inal, Jameel M; Schneider, Brigitte; Armanini, Marta; Schifferli, Jürg A

    2003-04-15

    Complement C2 receptor inhibitor trispanning (CRIT) is a Schistosoma protein that binds the human complement protein, C2. We recently showed that peptides based on the ligand binding region of CRIT inhibit the classical pathway (CP) of complement activation in human serum, using hemolytic assays and so speculated that on the parasite surface CRIT has the function of evading human complement. We now show that in vitro the C2-binding 11-aa C terminus of the first extracellular domain of CRIT, a 1.3-kDa peptide termed CRIT-H17, inhibits CP activation in a species-specific manner, inhibiting mouse and rat complement but not that from guinea pig. Hitherto, the ability of CRIT to regulate complement in vivo has not been assessed. In this study we show that by inhibiting the CP, CRIT-H17 is able to reduce immune complex-mediated inflammation (dermal reversed passive Arthus reaction) in BALB/c mice. Upon intradermal injection of CRIT-H17, and similarly with recombinant soluble complement receptor type 1, there was a 41% reduction in edema and hemorrhage, a 72% reduction in neutrophil influx, and a reduced C3 deposition. Furthermore, when H17 was administered i.v. at a 1 mg/kg dose, inflammation was reduced by 31%. We propose that CRIT-H17 is a potential therapeutic agent against CP complement-mediated inflammatory tissue destruction. PMID:12682267

  17. Crystal Structure of the Homo sapiens Kynureninase-3-Hydroxyhippuric Acid Inhibitor Complex: Insights into the Molecular Basis Of Kynureninase Substrate Specificity

    Energy Technology Data Exchange (ETDEWEB)

    Lima,Santiago; Kumar,Sunil; Gawandi,Vijay; Momany,Cory; Phillips,Robert S.; (Georgia)

    2009-02-23

    Homo sapiens kynureninase is a pyridoxal-5'-phosphate dependent enzyme that catalyzes the hydrolytic cleavage of 3-hydroxykynurenine to yield 3-hydroxyanthranilate and L-alanine as part of the tryptophan catabolic pathway leading to the de novo biosynthesis of NAD{sup +}. This pathway results in quinolinate, an excitotoxin that is an NMDA receptor agonist. High levels of quinolinate have been correlated with the etiology of neurodegenerative disorders such as AIDS-related dementia and Alzheimer's disease. We have synthesized a novel kynureninase inhibitor, 3-hydroxyhippurate, cocrystallized it with human kynureninase, and solved the atomic structure. On the basis of an analysis of the complex, we designed a series of His-102, Ser-332, and Asn-333 mutants. The H102W/N333T and H102W/S332G/N333T mutants showed complete reversal of substrate specificity between 3-hydroxykynurenine and L-kynurenine, thus defining the primary residues contributing to substrate specificity in kynureninases.

  18. A Model of Biological Attacks on a Realistic Population

    Science.gov (United States)

    Carley, Kathleen M.; Fridsma, Douglas; Casman, Elizabeth; Altman, Neal; Chen, Li-Chiou; Kaminsky, Boris; Nave, Demian; Yahja, Alex

    The capability to assess the impacts of large-scale biological attacks and the efficacy of containment policies is critical and requires knowledge-intensive reasoning about social response and disease transmission within a complex social system. There is a close linkage among social networks, transportation networks, disease spread, and early detection. Spatial dimensions related to public gathering places such as hospitals, nursing homes, and restaurants, can play a major role in epidemics [Klovdahl et. al. 2001]. Like natural epidemics, bioterrorist attacks unfold within spatially defined, complex social systems, and the societal and networked response can have profound effects on their outcome. This paper focuses on bioterrorist attacks, but the model has been applied to emergent and familiar diseases as well.

  19. 膜攻击复合物在特发性炎性肌肉病的表达研究%Expression of membrane attack complex in common idiopathic inflammatory myopathy

    Institute of Scientific and Technical Information of China (English)

    赵亚雯; 徐春晓; 刘靖; 左越焕; 张巍; 王朝霞; 袁云

    2015-01-01

    目的 总结膜攻击复合物在不同类型特发性炎性肌肉病的表达规律.方法 收集2011-2014年在北京大学第一医院收集的57例皮肌炎、37例多发性肌炎、9例散发性包涵体肌炎及15例抗信号识别颗粒(SRP)抗体免疫性坏死性肌病患者的肌肉活体组织标本,对其肌纤维和肌内衣毛细血管膜攻击复合物的表达率进行检测,采用x2检验或Fisher精确概率法进行统计学分析.结果 皮肌炎、多发性肌炎、散发性包涵体肌炎及抗SRP抗体免疫性坏死性肌病的肌肉膜攻击复合物表达总阳性率分别为75.4%(43/57)、86.5%(32/37)、4/9和13/15.肌纤维膜攻击复合物表达阳性率分别为50.9%(29/57)、81.1%(30/37)、3/9和13/15,肌内衣毛细血管膜攻击复合物表达阳性率分别为49.1% (28/57)、24.3%(9/37)、1/9和6/15.散发性包涵体肌炎的肌纤维和肌内衣毛细血管膜攻击复合物表达均低于其他类型炎性肌肉病,多发性肌炎和抗SRP抗体免疫性坏死性肌病的肌纤维膜攻击复合物表达阳性率差异无统计学意义,但均显著高于皮肌炎和散发性包涵体肌炎,皮肌炎和抗SRP抗体免疫性坏死性肌病的肌内衣毛细血管膜攻击复合物表达阳性率差异无统计学意义(x2=0.397,P=0.574),但均高于多发性肌炎和散发性包涵体肌炎.所有类型特发性炎性肌肉病的膜攻击复合物均存在区域性分布特点,其中11.6% (5/43)的皮肌炎患者出现束周分布.结论 膜攻击复合物在各种类型特发性炎性肌肉病的表达存在差异,抗SRP抗体免疫性坏死性肌病的膜攻击复合物表达兼具皮肌炎和多发性肌炎的特点.%Objective To analyze membrane attack complex (MAC) expression in different types of idiopathic inflammtory myopathy (IIM).Methods We enrolled 57 cases of dermatomyositis (DM) , 37 cases of polymyositis (PM) ,9 cases of sporadic inclusion body myositis (sIBM) and 15 cases of autoimmune necrotizing

  20. A binuclear complex constituted by diethyldithiocarbamate and copper(I) functions as a proteasome activity inhibitor in pancreatic cancer cultures and xenografts

    International Nuclear Information System (INIS)

    It is a therapeutic strategy for cancers including pancreatic to inhibit proteasome activity. Disulfiram (DSF) may bind copper (Cu) to form a DSF–Cu complex. DSF–Cu is capable of inducing apoptosis in cancer cells by inhibiting proteasome activity. DSF is rapidly converted to diethyldithiocarbamate (DDTC) within bodies. Copper(II) absorbed by bodies is reduced to copper(I) when it enters cells. We found that DDTC and copper(I) could form a binuclear complex which might be entitled DDTC–Cu(I), and it had been synthesized by us in the laboratory. This study is to investigate the anticancer potential of this complex on pancreatic cancer and the possible mechanism. Pancreatic cancer cell lines, SW1990, PANC-1 and BXPC-3 were used for in vitro assays. Female athymic nude mice grown SW1990 xenografts were used as animal models. Cell counting kit-8 (cck-8) assay and flow cytometry were used for analyzing apoptosis in cells. A 20S proteasome assay kit was used in proteasome activity analysis. Western blot (WB) and immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used in tumor sample analysis. The results suggest that DDTC–Cu(I) inhibit pancreatic cancer cell proliferation and proteasome activity in vitro and in vivo. Accumulation of ubiquitinated proteins, and increased p27 as well as decreased NF-κB expression were detected in tumor tissues of DDTC–Cu(I)-treated group. Our data indicates that DDTC–Cu(I) is an effective proteasome activity inhibitor with the potential to be explored as a drug for pancreatic cancer. - Highlights: • A new structure of DDTC–Cu(I) was reported for the first time. • DDTC–Cu(I) dissolved directly in water was for in vitro and in vivo uses. • DDTC–Cu(I) demonstrated significant anticancer effect in vitro and in vivo. • DDTC–Cu(I) is capable of inhibiting proteasome activity in vitro and in vivo

  1. A binuclear complex constituted by diethyldithiocarbamate and copper(I) functions as a proteasome activity inhibitor in pancreatic cancer cultures and xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jinbin, E-mail: hanjinbin@gmail.com [Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Shanghai Clinical Center, Chinese Academy of Sciences/Xuhui Central Hospital, Shanghai 200031 (China); Liu, Luming, E-mail: llm1010@163.com [Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Yue, Xiaoqiang [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Chang, Jinjia [Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Shi, Weidong; Hua, Yongqiang [Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)

    2013-12-15

    It is a therapeutic strategy for cancers including pancreatic to inhibit proteasome activity. Disulfiram (DSF) may bind copper (Cu) to form a DSF–Cu complex. DSF–Cu is capable of inducing apoptosis in cancer cells by inhibiting proteasome activity. DSF is rapidly converted to diethyldithiocarbamate (DDTC) within bodies. Copper(II) absorbed by bodies is reduced to copper(I) when it enters cells. We found that DDTC and copper(I) could form a binuclear complex which might be entitled DDTC–Cu(I), and it had been synthesized by us in the laboratory. This study is to investigate the anticancer potential of this complex on pancreatic cancer and the possible mechanism. Pancreatic cancer cell lines, SW1990, PANC-1 and BXPC-3 were used for in vitro assays. Female athymic nude mice grown SW1990 xenografts were used as animal models. Cell counting kit-8 (cck-8) assay and flow cytometry were used for analyzing apoptosis in cells. A 20S proteasome assay kit was used in proteasome activity analysis. Western blot (WB) and immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used in tumor sample analysis. The results suggest that DDTC–Cu(I) inhibit pancreatic cancer cell proliferation and proteasome activity in vitro and in vivo. Accumulation of ubiquitinated proteins, and increased p27 as well as decreased NF-κB expression were detected in tumor tissues of DDTC–Cu(I)-treated group. Our data indicates that DDTC–Cu(I) is an effective proteasome activity inhibitor with the potential to be explored as a drug for pancreatic cancer. - Highlights: • A new structure of DDTC–Cu(I) was reported for the first time. • DDTC–Cu(I) dissolved directly in water was for in vitro and in vivo uses. • DDTC–Cu(I) demonstrated significant anticancer effect in vitro and in vivo. • DDTC–Cu(I) is capable of inhibiting proteasome activity in vitro and in vivo.

  2. New Message Differences for Collision Attacks on MD4 and MD5

    Science.gov (United States)

    Sasaki, Yu; Wang, Lei; Kunihiro, Noboru; Ohta, Kazuo

    In 2005, collision resistance of several hash functions was broken by Wang et al. The strategy of determining message differences is the most important part of collision attacks against hash functions. So far, many researchers have tried to analyze Wang et al.'s method and proposed improved collision attacks. Although several researches proposed improved attacks, all improved results so far were based on the same message differences proposed by Wang et al. In this paper, we propose new message differences for collision attacks on MD4 and MD5. Our message differences of MD4 can generate a collision with complexity of less than two MD4 computations, which is faster than the original Wang et al.'s attack, and moreover, than the all previous attacks. This is the first result that improves the complexity of collision attack by using different message differences from Wang et al.'s. Regarding MD5, so far, no other message difference from Wang et al.'s is known. Therefore, study for constructing method of other message differences on MD5 should be interesting. Our message differences of MD5 generates a collision with complexity of 242 MD5 computations, which is slower than the latest best attack. However, since our attack needs only 1 bit difference, it has some advantages in terms of message freedom of collision messages.

  3. Impact of Degree Heterogeneity on Attack Vulnerability of Interdependent Networks.

    Science.gov (United States)

    Sun, Shiwen; Wu, Yafang; Ma, Yilin; Wang, Li; Gao, Zhongke; Xia, Chengyi

    2016-01-01

    The study of interdependent networks has become a new research focus in recent years. We focus on one fundamental property of interdependent networks: vulnerability. Previous studies mainly focused on the impact of topological properties upon interdependent networks under random attacks, the effect of degree heterogeneity on structural vulnerability of interdependent networks under intentional attacks, however, is still unexplored. In order to deeply understand the role of degree distribution and in particular degree heterogeneity, we construct an interdependent system model which consists of two networks whose extent of degree heterogeneity can be controlled simultaneously by a tuning parameter. Meanwhile, a new quantity, which can better measure the performance of interdependent networks after attack, is proposed. Numerical simulation results demonstrate that degree heterogeneity can significantly increase the vulnerability of both single and interdependent networks. Moreover, it is found that interdependent links between two networks make the entire system much more fragile to attacks. Enhancing coupling strength between networks can greatly increase the fragility of both networks against targeted attacks, which is most evident under the case of max-max assortative coupling. Current results can help to deepen the understanding of structural complexity of complex real-world systems. PMID:27609483

  4. Impact of Degree Heterogeneity on Attack Vulnerability of Interdependent Networks

    Science.gov (United States)

    Sun, Shiwen; Wu, Yafang; Ma, Yilin; Wang, Li; Gao, Zhongke; Xia, Chengyi

    2016-09-01

    The study of interdependent networks has become a new research focus in recent years. We focus on one fundamental property of interdependent networks: vulnerability. Previous studies mainly focused on the impact of topological properties upon interdependent networks under random attacks, the effect of degree heterogeneity on structural vulnerability of interdependent networks under intentional attacks, however, is still unexplored. In order to deeply understand the role of degree distribution and in particular degree heterogeneity, we construct an interdependent system model which consists of two networks whose extent of degree heterogeneity can be controlled simultaneously by a tuning parameter. Meanwhile, a new quantity, which can better measure the performance of interdependent networks after attack, is proposed. Numerical simulation results demonstrate that degree heterogeneity can significantly increase the vulnerability of both single and interdependent networks. Moreover, it is found that interdependent links between two networks make the entire system much more fragile to attacks. Enhancing coupling strength between networks can greatly increase the fragility of both networks against targeted attacks, which is most evident under the case of max-max assortative coupling. Current results can help to deepen the understanding of structural complexity of complex real-world systems.

  5. FLOODING ATTACK AWARE SECURE AODV

    Directory of Open Access Journals (Sweden)

    S. Madhavi

    2013-01-01

    Full Text Available Providing security in a Mobile Ad hoc Network (MANET is a challenging task due to its inherent nature. Flooding is a type of Denial of Service (DoS attack in MANET. Intentional flooding may lead to disturbances in the networking operation. This kind of attack consumes battery power, storage space and bandwidth. Flooding the excessive number of packets may degrade the performance of the network. This study considers hello flooding attack. As the hello packets are continuously flooded by the malicious node, the neighbor node is not able to process other packets. The functioning of the legitimate node is diverted and destroys the networking operation. Absence of hello packet during the periodical hello interval may lead to wrong assumption that the neighbor node has moved away. So one of the intermediate neighbor nodes sends Route Error (RERR message and the source node reinitiates the route discovery process. In a random fashion the hello interval values are changed and convey this information to other nodes in the network in a secured manner. This study identifies and prevents the flooding attack. This methodology considers the performance parameters such as packet delivery ratio, delay and throughput. This algorithm is implemented in Secure AODV and tested in ad hoc environment. The result of the proposed algorithm decreases the control overhead by 2%.

  6. Television journalism during terror attacks

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    2008-01-01

    reflected in the journalistic practices. The described norms form a coherent pattern if safeguarding the existing democracy and the general public is considered to be the main purpose. A coverage based on this pattern of norms can be compared to other forms of crisis management following attacks because...

  7. Television Journalism During Terror Attacks

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    This article views television news coverage of ongoing terrorist attacks and their immediate aftermath as a special genre within journalism, and describes norms connected with the genre. The description is based on qualitative analyses of the coverage on the major American networks in the fi rst ...

  8. [Polygraphy of a panic attack].

    Science.gov (United States)

    Noffke, H U; Roser, M

    2001-09-01

    We studied a 24-year old female patient with Type 1 diabetes mellitus suffering for 4 weeks from a major depressive episode combined with panic disorder without agoraphobia. A spontaneous panic attack was serendipitously recorded by polygraph while the subject was at rest. Electrocardiogram, finger blood-flow, respiratory rhythm and muscle tone (forearm, forehead) were recorded. A triphasic course consisting of a "dynamic phase" (appr. 80 s) preceded by a discrete "initial phase" (appr. 140 s) and a "declining phase" (appr. 180 s) was observed. The dynamic phase is characterized by an acute increase of fingertip vasoconstriction and heart rate. The patient was not aware of the panic attack before the dynamic phase. The recognisable central regulation confirms previously published findings indicating a sympathetic-norepinephrine activation at the beginning of the panic attack without activating the musculoskeletal system. Furthermore, a paradoxical phenomenon involving heart and respiratory rate was observed before the onset of anxiety, i.e. an increase of the heart rate and a simultaneous decline of the respiratory rate, suggesting a non-antagonistic regulation of the ergotropic-trophotropic system. The autonomic state of the patient points to a lability in homeostasis from which panic attacks as a form of CNS response could develop. PMID:11572106

  9. Automated Generation of Attack Trees

    DEFF Research Database (Denmark)

    Vigo, Roberto; Nielson, Flemming; Nielson, Hanne Riis

    2014-01-01

    are automatically inferred from a process algebraic specification in a syntax-directed fashion, encompassing a great many application domains and avoiding incurring systematically an exponential explosion. Moreover, we show how the standard propositional denotation of an attack tree can be used to phrase...

  10. On Linear Hulls, Statistical Saturation Attacks, PRESENT and a Cryptanalysis of PUFFIN

    DEFF Research Database (Denmark)

    Leander, Gregor

    2011-01-01

    We discuss complexities of advanced linear attacks. In particular, we argue why it is often more appropriate to examine the median of the complexity than the average value. Moreover, we apply our methods to the block ciphers PUFFIN and PRESENT. For PUFFIN, a 128 bit key cipher, we present an attack...... which breaks the cipher for at least a quarter of the keys with a complexity less than 258. In the case of PRESENT we show that the design is sound. The design criteria are sufficient to ensure the resistance against linear attacks, taking into account the notion of linear hulls. Finally, we show...... that statistical saturation attacks and multi dimensional linear attacks are almost identical....

  11. Assessing Terrorist Motivations for Attacking Critical Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Ackerman, G; Abhayaratne, P; Bale, J; Bhattacharjee, A; Blair, C; Hansell, L; Jayne, A; Kosal, M; Lucas, S; Moran, K; Seroki, L; Vadlamudi, S

    2006-12-04

    Certain types of infrastructure--critical infrastructure (CI)--play vital roles in underpinning our economy, security and way of life. These complex and often interconnected systems have become so ubiquitous and essential to day-to-day life that they are easily taken for granted. Often it is only when the important services provided by such infrastructure are interrupted--when we lose easy access to electricity, health care, telecommunications, transportation or water, for example--that we are conscious of our great dependence on these networks and of the vulnerabilities that stem from such dependence. Unfortunately, it must be assumed that many terrorists are all too aware that CI facilities pose high-value targets that, if successfully attacked, have the potential to dramatically disrupt the normal rhythm of society, cause public fear and intimidation, and generate significant publicity. Indeed, revelations emerging at the time of this writing about Al Qaida's efforts to prepare for possible attacks on major financial facilities in New York, New Jersey, and the District of Columbia remind us just how real and immediate such threats to CI may be. Simply being aware that our nation's critical infrastructure presents terrorists with a plethora of targets, however, does little to mitigate the dangers of CI attacks. In order to prevent and preempt such terrorist acts, better understanding of the threats and vulnerabilities relating to critical infrastructure is required. The Center for Nonproliferation Studies (CNS) presents this document as both a contribution to the understanding of such threats and an initial effort at ''operationalizing'' its findings for use by analysts who work on issues of critical infrastructure protection. Specifically, this study focuses on a subsidiary aspect of CI threat assessment that has thus far remained largely unaddressed by contemporary terrorism research: the motivations and related factors that

  12. Generic attack approaches for industrial control systems.

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, David P.

    2006-01-01

    This report suggests a generic set of attack approaches that are expected to be used against Industrial Control Systems that have been built according to a specific reference model for control systems. The posed attack approaches are ordered by the most desirable, based upon the goal of an attacker. Each attack approach is then graded by the category of adversary that would be capable of utilizing that attack approach. The goal of this report is to identify necessary levels of security required to prevent certain types of attacks against Industrial Control Systems.

  13. Attacks and countermeasures on AES and ECC

    DEFF Research Database (Denmark)

    Tange, Henrik; Andersen, Birger

    2013-01-01

    AES (Advanced Encryption Standard) is widely used in LTE and Wi-Fi communication systems. AES has recently been exposed to new attacks which have questioned the overall security of AES. The newest attack is a so called biclique attack, which is using the fact that the content of the state array...... is foreseeable while the rounds are performed. ECC (Elliptic Curve Cryptography) is used as a public key crypto system with the key purpose of creating a private shared between two participants in a communication network. Attacks on ECC include the Pohlig-Hellman attack and the Pollard's rho attack. Furthermore...

  14. Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Li, Juan [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Qiu, Zhuibai [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Xia, Zheng [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Li, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Yu, Lining; Chen, Hailin; Chen, Jianxing [NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Xie, Qiong, E-mail: xiejoanxq@gmail.com [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Chen, Hongzhuan, E-mail: yaoli@shsmu.edu.cn [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China)

    2012-10-01

    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

  15. Trypanosoma cruzi trans-sialidase in complex with a neutralizing antibody: structure/function studies towards the rational design of inhibitors.

    Directory of Open Access Journals (Sweden)

    Alejandro Buschiazzo

    2012-01-01

    Full Text Available Trans-sialidase (TS, a virulence factor from Trypanosoma cruzi, is an enzyme playing key roles in the biology of this protozoan parasite. Absent from the mammalian host, it constitutes a potential target for the development of novel chemotherapeutic drugs, an urgent need to combat Chagas' disease. TS is involved in host cell invasion and parasite survival in the bloodstream. However, TS is also actively shed by the parasite to the bloodstream, inducing systemic effects readily detected during the acute phase of the disease, in particular, hematological alterations and triggering of immune cells apoptosis, until specific neutralizing antibodies are elicited. These antibodies constitute the only known submicromolar inhibitor of TS's catalytic activity. We now report the identification and detailed characterization of a neutralizing mouse monoclonal antibody (mAb 13G9, recognizing T. cruzi TS with high specificity and subnanomolar affinity. This mAb displays undetectable association with the T. cruzi superfamily of TS-like proteins or yet with the TS-related enzymes from Trypanosoma brucei or Trypanosoma rangeli. In immunofluorescence assays, mAb 13G9 labeled 100% of the parasites from the infective trypomastigote stage. This mAb also reduces parasite invasion of cultured cells and strongly inhibits parasite surface sialylation. The crystal structure of the mAb 13G9 antigen-binding fragment in complex with the globular region of T. cruzi TS was determined, revealing detailed molecular insights of the inhibition mechanism. Not occluding the enzyme's catalytic site, the antibody performs a subtle action by inhibiting the movement of an assisting tyrosine (Y₁₁₉, whose mobility is known to play a key role in the trans-glycosidase mechanism. As an example of enzymatic inhibition involving non-catalytic residues that occupy sites distal from the substrate-binding pocket, this first near atomic characterization of a high affinity inhibitory molecule

  16. Subtle Regulation of Potato Acid Invertase Activity by a Protein Complex of Invertase, Invertase Inhibitor, and SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE.

    Science.gov (United States)

    Lin, Yuan; Liu, Tengfei; Liu, Jun; Liu, Xun; Ou, Yongbin; Zhang, Huiling; Li, Meng; Sonnewald, Uwe; Song, Botao; Xie, Conghua

    2015-08-01

    Slowing down cold-induced sweetening (CIS) of potato (Solanum tuberosum) tubers is of economic importance for the potato industry to ensure high-quality products. The conversion of sucrose to reducing sugars by the acid invertase StvacINV1 is thought to be critical for CIS. Identification of the specific StvacINV1 inhibitor StInvInh2B and the α- and β-subunits of the interacting protein SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE from the wild potato species Solanum berthaultii (SbSnRK1) has led to speculation that invertase activity may be regulated via a posttranslational mechanism that remains to be elucidated. Using bimolecular fluorescence complementation assays, this study confirmed the protein complex by pairwise interactions. In vitro kinase assays and protein phosphorylation analysis revealed that phosphorylation of SbSnRK1α is causal for StvacINV1 activity and that its active form blocks the inhibition of StInvInh2B by SbSnRK1β, whereas its inactive form restores the function of SbSnRK1β that prevents StInvInh2B from repressing StvacINV1. Overexpression of SbSnRK1α in CIS-sensitive potato confirmed that SbSnRK1α has significant effects on acid invertase-associated sucrose degradation. A higher level of SbSnRK1α expression was accompanied by elevated SbSnRK1α phosphorylation, reduced acid invertase activity, a higher sucrose-hexose ratio, and improved chip color. Our results lend new insights into a subtle regulatory mode of invertase activity and provide a novel approach for potato CIS improvement. PMID:26134163

  17. Loss of Tuberous Sclerosis Complex 2 (TSC2) Is Frequent in Hepatocellular Carcinoma and Predicts Response to mTORC1 Inhibitor Everolimus.

    Science.gov (United States)

    Huynh, Hung; Hao, Huai-Xiang; Chan, Stephen L; Chen, David; Ong, Richard; Soo, Khee Chee; Pochanard, Panisa; Yang, David; Ruddy, David; Liu, Manway; Derti, Adnan; Balak, Marissa N; Palmer, Michael R; Wang, Yan; Lee, Benjamin H; Sellami, Dalila; Zhu, Andrew X; Schlegel, Robert; Huang, Alan

    2015-05-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and hyperactivation of mTOR signaling plays a pivotal role in HCC tumorigenesis. Tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2, functions as a negative regulator of mTOR signaling. In the current study, we discovered that TSC2 loss-of-function is common in HCC. TSC2 loss was found in 4 of 8 HCC cell lines and 8 of 28 (28.6%) patient-derived HCC xenografts. TSC2 mutations and deletions are likely to be the underlying cause of TSC2 loss in HCC cell lines, xenografts, and primary tumors for most cases. We further demonstrated that TSC2-null HCC cell lines and xenografts had elevated mTOR signaling and, more importantly, were significantly more sensitive to RAD001/everolimus, an mTORC1 inhibitor. These preclinical findings led to the analysis of TSC2 status in HCC samples collected in the EVOLVE-1 clinical trial of everolimus using an optimized immunohistochemistry assay and identified 15 of 139 (10.8%) samples with low to undetectable levels of TSC2. Although the sample size is too small for formal statistical analysis, TSC2-null/low tumor patients who received everolimus tended to have longer overall survival than those who received placebo. Finally, we performed an epidemiology survey of more than 239 Asian HCC tumors and found the frequency of TSC2 loss to be approximately 20% in Asian HBV(+) HCC. Taken together, our data strongly argue that TSC2 loss is a predictive biomarker for the response to everolimus in HCC patients. PMID:25724664

  18. Finding multi-step attacks in computer networks using heuristic search and mobile ambients

    NARCIS (Netherlands)

    Franqueira, Virginia Nunes Leal

    2009-01-01

    An important aspect of IT security governance is the proactive and continuous identification of possible attacks in computer networks. This is complicated due to the complexity and size of networks, and due to the fact that usually network attacks are performed in several steps. This thesis proposes

  19. New related-key rectangle attacks on reduced AES-192 and AES-256

    Institute of Scientific and Technical Information of China (English)

    WEI YongZhuang; HU YuPu

    2009-01-01

    In this paper, we examine the security of reduced AES-192 and AES-256 against related-key rectangle attacks by exploiting the weakness in the AES key schedule. We find the following two new attacks: 9-round reduced AES-192 with 4 related keys, and 10-round reduced AES-256 with 4 related keys. Our results show that related-key rectangle attack with 4 related keys on 9-round reduced AES-192 requires a data complexity of about 2101 chosen plaintexts and a time complexity of about 2174.8 encryptions, and moreover, related-key rectangle attack with 4 related keys on 10-round reduced AES-256 requires a data complexity of about 297.5 chosen plaintexts and a time complexity of about 2254 encryptions. These attacks are the first known attacks on 9-round reduced AES-192 and 10-round reduced AES-256 with only 4 related keys. Furthermore, we give an improvement of the 10-round reduced AES-192 attack presented at FSE2007, which reduces both the data complexity and the time complexity.

  20. A simple coherent attack and practical security of differential phase shift quantum cryptography

    Science.gov (United States)

    Kronberg, D. A.

    2014-02-01

    The differential phase shift quantum key distribution protocol reveals good security against such powerful attacks as unambiguous state discrimination and beam splitting attacks. Its complete security analysis is complex due to high dimensions of the supposed spaces and density operators. In this paper, we consider a particular and conceptually simple coherent attack, available in practical implementations. The main condition for this attack is the length of used coherent state tuples of order 8-12. We show that under this condition, no high level of practical distance between legitimate users can be achieved.

  1. Multidimensional zero-correlation attacks on lightweight block cipher HIGHT: Improved cryptanalysis of an ISO standard

    DEFF Research Database (Denmark)

    Wen, Long; Wang, Meiqin; Bogdanov, Andrey;

    2014-01-01

    results on HIGHT, its security evaluation against the recent zero-correlation linear attacks is still lacking. At the same time, the Feistel-type structure of HIGHT suggests that it might be susceptible to this type of cryptanalysis. In this paper, we aim to bridge this gap. We identify zero......-correlation linear approximations over 16 rounds of HIGHT. Based upon those, we attack 27-round HIGHT (round 4 to round 30) with improved time complexity and practical memory requirements. This attack of ours is the best result on HIGHT to date in the classical single-key setting. We also provide the first attack...

  2. Medicines to Treat Heart Attack

    Science.gov (United States)

    ... other medicines, such as a diuretic or a beta blocker. Side effects. ACE inhibitors don’t usually cause ... and tell you exactly how to take it. Beta Blockers Beta blockers are a group of drugs that ...

  3. Perfection of Recent Attacks using IP

    Directory of Open Access Journals (Sweden)

    A. RENGARAJAN

    2012-02-01

    Full Text Available The Internet threat monitoring (ITM systems have been deployed to detect widespread attacks on the Internet in recent years. However, the effectiveness of ITM systems critically depends on the confidentiality of the location of their monitors. If adversaries learn the monitor locations of an ITM system, they can bypass the monitors and focus on the uncovered IP address space without being detected. In this paper, we study a new class of attacks, the invisible LOCalization (iLOC attack. The iLOC attack can accurately and invisibly localize monitors of ITM systems. In the iLOC attack, the attacker launches low-rate port-scan traffic, encoded with a selected pseudo noise code (PN-code, to targeted networks. While the secret PN-code is invisible to others, the attacker can accurately determine the existence of monitors in the targeted networks based on whether the PN-code is embedded in the report data queried from the data center of the ITM system. We formally analyze the impact of various parameters on attack effectiveness. We implement the iLOC attack and conduct the performance evaluation on a real-world ITM system to demonstrate the possibility of such attacks. We also conduct extensive simulations on the iLOC attack using real-world traces. Our data show that the iLOC attack can accurately identify monitors while being invisible to ITM systems. Finally, we present a set of guidelines to counteract the iLOC attack.

  4. Measurement of homonuclear three-bond J(HNH{alpha}) coupling constants in unlabeled peptides complexed with labeled proteins: Application to a decapeptide inhibitor bound to the proteinase domain of the NS3 protein of hepatitis C virus (HCV)

    Energy Technology Data Exchange (ETDEWEB)

    Cicero, Daniel O.; Barbato, Gaetano; Koch, Uwe; Ingallinella, Paolo; Bianchi, Elisabetta; Sambucini, Sonia; Neddermann, Petra; De Francesco, Raffaele; Pessi, Antonello; Bazzo, Renzo

    2001-05-15

    A new isotope-filtered experiment has been designed to measure homonuclear three-bond J(H{sup N}H{sup {alpha}}) coupling constants of unlabeled peptides complexed with labeled proteins. The new experiment is based on the 3D HNHA pulse scheme, and belongs to the 'quantitative J-correlation' type. It has been applied to a decapeptide inhibitor bound to the proteinase domain of the NS3 protein of human hepatitis C virus (HCV)

  5. Ontology based Intrusion Detection System in Wireless Sensor Network for Active Attacks

    Directory of Open Access Journals (Sweden)

    Naheed Akhter

    2016-06-01

    Full Text Available WSNs are vulnerable to attacks and have deemed special attention for developing mechanism for securing against various threats that could effect the overall infrastructure. WSNs are open to miscellaneous classes of attacks and security breaches are intolerable in WSNs. Threats like untrusted data transmissions, settlement in open and unfavorable environments are still open research issues. Safekeeping is an essential and complex requirement in WSNs. These issues raise the need to develop a security-based mechanism for Wireless Sensor Network to categorize the different attacks based on their relevance. A detailed survey of active attacks is highlighted based on the nature and attributes of those attacks. An Ontology based mechanism is developed and tested for active attack in WSNs.

  6. Stochastic Model of TCP SYN Attacks

    Directory of Open Access Journals (Sweden)

    Simona Ramanauskaitė

    2011-08-01

    Full Text Available A great proportion of essential services are moving into internet space making the threat of DoS attacks even more actual. To estimate the real risk of some kind of denial of service (DoS attack in real world is difficult, but mathematical and software models make this task easier. In this paper we overview the ways of implementing DoS attack models and offer a stochastic model of SYN flooding attack. It allows evaluating the potential threat of SYN flooding attacks, taking into account both the legitimate system flow as well as the possible attack power. At the same time we can assess the effect of such parameters as buffer capacity, open connection storage in the buffer or filte­ring efficiency on the success of different SYN flooding attacks. This model can be used for other type of memory depletion denial of service attacks.Article in Lithuanian

  7. Heart attack - what to ask your doctor

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000231.htm Heart attack - what to ask your doctor To use the ... features on this page, please enable JavaScript. A heart attack occurs when blood flow to a part of ...

  8. Fat May Not Hike Heart Attack Risk

    Science.gov (United States)

    ... news/fullstory_160179.html Fat May Not Hike Heart Attack Risk: Study But it does raise diabetes risk, ... that obesity may not increase the risk of heart attack or premature death. Their study of identical twins ...

  9. Being active after a heart attack (image)

    Science.gov (United States)

    ... best activity when you start exercising after a heart attack. Start slowly, and increase the amount of time ... best activity when you start exercising after a heart attack. Start slowly, and increase the amount of time ...

  10. Protecting Cryptographic Memory against Tampering Attack

    DEFF Research Database (Denmark)

    Mukherjee, Pratyay

    . In practice such attacks can be executed easily, e.g. by heating the device, as substantiated by numerous works in the past decade. Tampering attacks are a class of such physical attacks where the attacker can change the memory/computation, gains additional (non-black-box) knowledge by interacting......In this dissertation we investigate the question of protecting cryptographic devices from tampering attacks. Traditional theoretical analysis of cryptographic devices is based on black-box models which do not take into account the attacks on the implementations, known as physical attacks...... with the faulty device and then tries to break the security. Prior works show that generically approaching such problem is notoriously difficult. So, in this dissertation we attempt to solve an easier question, known as memory-tampering, where the attacker is allowed tamper only with the memory of the device...

  11. Diabetes Ups Risk of Heart Attack Death

    Science.gov (United States)

    ... 159557.html Diabetes Ups Risk of Heart Attack Death Study points to need for better coordinated care, ... people with diabetes have a higher risk of death after a heart attack. "We knew that following ...

  12. Intermittent hypoendorphinaemia in migraine attack.

    Science.gov (United States)

    Baldi, E; Salmon, S; Anselmi, B; Spillantini, M G; Cappelli, G; Brocchi, A; Sicuteri, F

    1982-06-01

    Beta-endorphin (RIA method, previous chromatographic extraction) was evaluated in plasma of migraine sufferers in free periods and during attacks. Decreased levels of the endogenous opioid peptide were found in plasma sampled during the attacks but not in free periods. Even chronic headache sufferers exhibited significantly lowered levels of beta-endorphin, when compared with control subjects with a negative personal and family history of head pains. The mechanism of the hypoendorphinaemia is unknown: lowered levels of the neuropeptide, which controls nociception, vegetative functions and hedonia, could be important in a syndrome such as migraine, characterized by pain, dysautonomia and anhedonia. The impairment of monoaminergic synapses ("empty neuron" condition) constantly present in sufferers from serious headaches, could be due to the fact that opioid neuropeptides, because of a receptoral or metabolic impairment, poorly modulate the respective monoaminergic neurons, resulting in imbalance of synaptic neurotransmission. PMID:6290072

  13. A Robust Localization in Wireless Sensor Networks against Wormhole Attack

    Directory of Open Access Journals (Sweden)

    Yanchao Niu

    2012-01-01

    Full Text Available Wormhole attack is one of the most devastating threats for range-free localization in wireless sensor networks. To address this issue, we propose a robust localization scheme in wireless sensor networks against wormhole attack, called ConSetLoc, which neither complicated distance measuring devices nor extra complex encrypting algorithms is necessary. With the relationship between hop counts and geographic distance of sensor nodes in the deployment territory, we design a partition method of consistent anchors sets by the convex constraints in geometry which can reduce the effect of bad measurements on estimates,  and then present a filtering strategy for the candidate locations with these anchors sets. In addition, we conduct simulation experiments for performance evaluation and the results demonstrate the proposed ConSetLoc can estimate the locations for most of sensor nodes with good accuracy and stability when wormhole attack exists in the network.

  14. Computing Preferred Extensions for Argumentation Systems with Sets of Attacking

    DEFF Research Database (Denmark)

    Nielsen, Søren Holbech; Parsons, Simon

    2006-01-01

    The hitherto most abstract, and hence general, argumentation system, is the one described by Dung in a paper from 1995. This framework does not allow for joint attacks on arguments, but in a recent paper we adapted it to support such attacks, and proved that this adapted framework enjoyed the same...... formal properties as that of Dung. One problem posed by Dung's original framework, which was neglected for some time, is how to compute preferred extensions of the argumentation systems. However, in 2001, in a paper by Doutre and Mengin, a procedure was given for enumerating preferred extensions...... for these systems. In this paper we propose a method for enumerating preferred extensions of the potentially more complex systems, where joint attacks are allowed. The method is inspired by the one given by Doutre and Mengin....

  15. A Case Of Transient Ischemic Attack Presenting As Hemichroea

    Directory of Open Access Journals (Sweden)

    Hasan Hüseyin Özdemir

    2013-12-01

    Full Text Available Chorea is defined as; involuntary movements of the distal parts of limbs which have arrhythmic, rapid, bouncing or smooth, simple or complex properties. Choreiform movements occur when putamen, globus pallidus and subthalamic nucleus are affected. Chorea can be observed during the course of metabolic and vascular diseases, neurodegenerative or hereditary diseases. Chorea may be a rare symptom of cerebral hypoperfusion. Transient ischemic attack is an event that occurs in short term characterized by a temporary ischemia of brain. A wide variety of symptoms can be seen depending on the localization of cerebral hypoperfusion. Hemichorea is a very rare finding observed during transient ischemic attacks. In this article hemichorea in a case of symptomatic transient ischemic attack is discussed with relevant literature.

  16. DULOXETINE-RELATED PANIC ATTACKS

    OpenAIRE

    Sabljić, Vladimir; Rakun, Radmir; Ružić, Klementina; Grahovac, Tanja

    2011-01-01

    Side-effects arising on the grounds of antidepressant administration pose as a substantial obstacle hindering successful depressive disorder treatment. Side-effects, especially those severe or those manifested through dramatic clinical presentations such as panic attacks, make the treatment far more difficult and shake patients’ trust in both the treatment and the treating physician. This case report deals with a patient experiencing a moderately severe depressive episode, who respon...

  17. Where can an Insider attack?

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, René Rydhof; Nielson, Flemming

    2006-01-01

    By definition, an insider has better access, is more trusted, and has better information about internal procedures, high-value targets, and potential weak spots in the security, than an outsider. Consequently, an insider attack has the potential to cause significant, even catastrophic, damage...... of the modelled systems. Our analysis of processes identifies which actions may be performed by whom, at which locations, accessing which data. This allows to compute a superset of audit results---before an incident occurs....

  18. Biomechanics of knife stab attacks.

    Science.gov (United States)

    Chadwick, E K; Nicol, A C; Lane, J V; Gray, T G

    1999-10-25

    Equipment, materials and methods for the measurement of the biomechanical parameters governing knife stab attacks have been developed and data have been presented that are relevant to the improvement of standards for the testing of stab-resistant materials. A six-camera Vicon motion analysis system was used to measure velocity, and derive energy and momentum during the approach phase of the attack and a specially developed force-measuring knife was used to measure three-dimensional forces and torque during the impact phase. The body segments associated with the knife were modelled as a series of rigid segments: trunk, upper arm, forearm and hand. The velocities of these segments, together with knowledge of the mass distribution from biomechanical tables, allowed the calculation of the individual segment energy and momentum values. The instrumented knife measured four components of load: axial force (along the length of the blade), cutting force (parallel to the breadth of the blade), lateral force (across the blade) and torque (twisting action) using foil strain gauges. Twenty volunteers were asked to stab a target with near maximal effort. Three styles of stab were used: a short thrust forward, a horizontal style sweep around the body and an overhand stab. These styles were chosen based on reported incidents, providing more realistic data than had previously existed. The 95th percentile values for axial force and energy were 1885 N and 69 J, respectively. The ability of current test methods to reproduce the mechanical parameters measured in human stab attacks has been assessed. It was found that current test methods could reproduce the range of energy and force values measured in the human stab attacks, although the simulation was not accurate in some respects. Non-axial force and torque values were also found to be significant in the human tests, but these are not reproduced in the standard mechanical tests.

  19. Coyote Attacks: An Increasing Suburban Problem

    OpenAIRE

    Timm, Robert M.; Baker, Rex O.; Bennett, Joe R.; Coolahan, Craig C.

    2004-01-01

    Coyote attacks on humans and pets have increased within the past 5 years in California. We discuss documented occurrences of coyote aggression and attacks on people, using data from USDA Wildlife Services, the California Department of Fish & Game, and other sources. Forty-eight such attacks on children and adults were verified from 1998 through 2003, compared to 41 attacks during the period 1988 through 1997; most incidents occurred in Southern California near the suburban-wildland interfac...

  20. Sybil attack in Wireless Sensor Network

    OpenAIRE

    Abirami.K; Santhi.B

    2013-01-01

    Wireless network is very susceptible to different types of attack. The main attack is Sybil attack, which allows forming other attacks on the network. Security is very important to the wireless network. In wireless sensor network, to verify node identities by cryptographic authentication but this is not easy because sensor node which contains limited resources. Therefore the current research is going on how to handling the situation of different traffic levels and transmission power for secur...

  1. Sybil attack in Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Abirami.K

    2013-04-01

    Full Text Available Wireless network is very susceptible to different types of attack. The main attack is Sybil attack, which allows forming other attacks on the network. Security is very important to the wireless network. In wireless sensor network, to verify node identities by cryptographic authentication but this is not easy because sensor node which contains limited resources. Therefore the current research is going on how to handling the situation of different traffic levels and transmission power for security.

  2. Distributed Denial of Service (DDoS) Attacks Detection Mechanism

    CERN Document Server

    Kumarasamy, Saravanan

    2012-01-01

    Pushback is a mechanism for defending against Distributed Denial-of-Service (DDoS) attacks. DDoS attacks are treated as a congestion-control problem, but because most such congestion is caused by malicious hosts not obeying traditional end-to-end congestion control, the problem must be handled by the routers. Functionality is added to each router to detect and preferentially drop packets that probably belong to an attack. Upstream routers are also notified to drop such packets in order that the router's resources be used to route legitimate traffic hence term pushback. Client puzzles have been advocated as a promising countermeasure to DoS attacks in the recent years. In order to identify the attackers, the victim server issues a puzzle to the client that sent the traffic. When the client is able to solve the puzzle, it is assumed to be authentic and the traffic from it is allowed into the server. If the victim suspects that the puzzles are solved by most of the clients, it increases the complexity of the puz...

  3. Timing and hamming weight attacks on minimal cost encryption scheme

    Institute of Scientific and Technical Information of China (English)

    YUAN Zheng; WANG Wei; ZHANG Hua; WEN Qiao-yan

    2009-01-01

    The timing and Hamming weight attacks on the data encryption standard (DES) cryptosystem for minimal cost encryption scheme is presented in this article. In the attack, timing information on encryption processing is used to select and collect effective plaintexts for attack. Then the collected plaintexts are utilized to infer the expanded key differences of the secret key, from which most bits of the expanded secret key are recovered. The remaining bits of the expanded secret key are deduced by the correlations between Hamming weight values of the input of the S-boxes in the first-round. Finally, from the linear relation of the encryption time and the secret key's Hamming weight, the entire 56 bits of the secret key are thoroughly recovered. Using the attack, the minimal cost encryption scheme can be broken with 223 known plaintexts and about 221 calculations at a success rate a>99%. The attack has lower computing complexity, and the method is more effective than other previous methods.

  4. A Novel Attack against Android Phones

    CERN Document Server

    Backes, Michael; von Styp-Rekowsky, Philipp

    2011-01-01

    In the first quarter of 2011, Android has become the top-selling operating system for smartphones. In this paper, we present a novel, highly critical attack that allows unprompted installation of arbitrary applications from the Android Market. Our attack is based on a single malicious application, which, in contrast to previously known attacks, does not require the user to grant it any permissions.

  5. Attack Tree Generation by Policy Invalidation

    DEFF Research Database (Denmark)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, Rene Rydhof;

    2015-01-01

    through brainstorming of experts. In this work we formalize attack tree generation including human factors; based on recent advances in system models we develop a technique to identify possible attacks analytically, including technical and human factors. Our systematic attack generation is based...

  6. Understand Your Risk of Heart Attack

    Science.gov (United States)

    ... Stroke More Understand Your Risks to Prevent a Heart Attack Updated:Aug 2,2016 Knowledge is power, so ... medication. This content was last reviewed June 2016. Heart Attack • Home • About Heart Attacks Acute Coronary Syndrome (ACS) • ...

  7. Cyberprints: Identifying Cyber Attackers by Feature Analysis

    Science.gov (United States)

    Blakely, Benjamin A.

    2012-01-01

    The problem of attributing cyber attacks is one of increasing importance. Without a solid method of demonstrating the origin of a cyber attack, any attempts to deter would-be cyber attackers are wasted. Existing methods of attribution make unfounded assumptions about the environment in which they will operate: omniscience (the ability to gather,…

  8. On Mitigating Distributed Denial of Service Attacks

    Science.gov (United States)

    Gao, Zhiqiang

    2006-01-01

    Denial of service (DoS) attacks and distributed denial of service (DDoS) attacks are probably the most ferocious threats in the Internet, resulting in tremendous economic and social implications/impacts on our daily lives that are increasingly depending on the well-being of the Internet. How to mitigate these attacks effectively and efficiently…

  9. Green Plant Extract as a passivationpromoting Inhibitor for Reinforced Concrete

    OpenAIRE

    Abdulrahman A. S.; Mohammad Ismail

    2011-01-01

    The present corrosion inhibitors in market for the protection of steel reinforcement in concrete exposed to chloride attack are toxic to the environment and compromises sustainability drives. There is the needs to develop inhibitor that are eco-friendly and sustainable. In this work the ability of hydrophobic green plant extracts inhibitor (Bambusa arundinacea) to repassivates the chloride induced corrosion of steel was studied. Its efficacy and effectiveness was also compared with calcium ni...

  10. Identification of quercitrin as an inhibitor of the p90 S6 ribosomal kinase (RSK): structure of its complex with the N-terminal domain of RSK2 at 1.8 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Derewenda, Urszula; Artamonov, Mykhaylo; Szukalska, Gabriela; Utepbergenov, Darkhan; Olekhnovich, Natalya [University of Virginia, Charlottesville, VA 22908-0736 (United States); Parikh, Hardik I.; Kellogg, Glen E. [Virginia Commonwealth University, Richmond, VA 23298-0540 (United States); Somlyo, Avril V.; Derewenda, Zygmunt S., E-mail: zsd4n@virginia.edu [University of Virginia, Charlottesville, VA 22908-0736 (United States)

    2013-02-01

    The crystal structure of quercitrin, a naturally occurring flavonol glycoside, has been determined in a complex with the N-terminal kinase domain of murine RSK2. The structure revealed that quercitrin inhibits the RSK2 kinase in the same fashion as another known inhibitor, SL0101. Members of the RSK family of kinases constitute attractive targets for drug design, but a lack of structural information regarding the mechanism of selective inhibitors impedes progress in this field. The crystal structure of the N-terminal kinase domain (residues 45–346) of mouse RSK2, or RSK2{sup NTKD}, has recently been described in complex with one of only two known selective inhibitors, a rare naturally occurring flavonol glycoside, kaempferol 3-O-(3′′,4′′-di-O-acetyl-α-l-rhamnopyranoside), known as SL0101. Based on this structure, it was hypothesized that quercitrin (quercetin 3-O-α-l-rhamnopyranoside), a related but ubiquitous and inexpensive compound, might also act as an RSK inhibitor. Here, it is demonstrated that quercitrin binds to RSK2{sup NTKD} with a dissociation constant (K{sub d}) of 5.8 µM as determined by isothermal titration calorimetry, and a crystal structure of the binary complex at 1.8 Å resolution is reported. The crystal structure reveals a very similar mode of binding to that recently reported for SL0101. Closer inspection shows a number of small but significant differences that explain the slightly higher K{sub d} for quercitrin compared with SL0101. It is also shown that quercitrin can effectively substitute for SL0101 in a biological assay, in which it significantly suppresses the contractile force in rabbit pulmonary artery smooth muscle in response to Ca{sup 2+}.

  11. Whispering through DDoS attack

    OpenAIRE

    Miralem Mehic; Jiri Slachta; Miroslav Voznak

    2016-01-01

    Denial of service (DoS) attack is an attempt of the attacker to disable victim's machine by depleting network or computing resources. If this attack is performed with more than one machine, it is called distributed denial of service (DDoS) attack. Covert channels are those channels which are used for information transmission even though they are neither designed nor intended to transfer information at all. In this article, we investigated the possibility of using of DDoS attack for purposes o...

  12. Methods of Identifying and Preventing SQL Attacks

    Directory of Open Access Journals (Sweden)

    Bojken Shehu

    2012-11-01

    Full Text Available The paper begins by identifying the organizations which are vulnerable to the SQL attack referred to as an SQL injection attack. The term SQL injection attack is defined and a diagram is used to illustrate the way that attack occurs. In another section, the paper identifies the methods used to detect an attack to SQL, whereby the techniques are discussed extensively using relevant diagrams for illustration. The other sections cover the preventive methods, where the methods are also discussed with an illustration using diagrams.

  13. Lightweight Distance Bounding Protocol against Relay Attacks

    Science.gov (United States)

    Kim, Jin Seok; Cho, Kookrae; Yum, Dae Hyun; Hong, Sung Je; Lee, Pil Joong

    Traditional authentication protocols are based on cryptographic techniques to achieve identity verification. Distance bounding protocols are an enhanced type of authentication protocol built upon both signal traversal time measurement and cryptographic techniques to accomplish distance verification as well as identity verification. A distance bounding protocol is usually designed to defend against the relay attack and the distance fraud attack. As there are applications to which the distance fraud attack is not a serious threat, we propose a streamlined distance bounding protocol that focuses on the relay attack. The proposed protocol is more efficient than previous protocols and has a low false acceptance rate under the relay attack.

  14. NETWORK SECURITY ATTACKS. ARP POISONING CASE STUDY

    Directory of Open Access Journals (Sweden)

    Luminiţa DEFTA

    2010-12-01

    Full Text Available Arp poisoning is one of the most common attacks in a switched network. A switch is a network device that limits the ability of attackers that use a packet sniffer to gain access to information from internal network traffic. However, using ARP poisoning the traffic between two computers can be intercepted even in a network that uses switches. This method is known as man in the middle attack. With this type of attack the affected stations from a network will have invalid entries in the ARP table. Thus, it will contain only the correspondence between the IP addresses of the stations from the same network and a single MAC address (the station that initiated the attack. In this paper we present step by step the initiation of such an attack in a network with three computers. We will intercept the traffic between two stations using the third one (the attacker.

  15. SQL Injection Attacks and Defense

    CERN Document Server

    Clarke, Justin

    2012-01-01

    SQL Injection Attacks and Defense, First Edition: Winner of the Best Book Bejtlich Read Award "SQL injection is probably the number one problem for any server-side application, and this book unequaled in its coverage." -Richard Bejtlich, Tao Security blog SQL injection represents one of the most dangerous and well-known, yet misunderstood, security vulnerabilities on the Internet, largely because there is no central repository of information available for penetration testers, IT security consultants and practitioners, and web/software developers to turn to for help. SQL Injection Att

  16. What Are the Symptoms of a Heart Attack?

    Science.gov (United States)

    ... on Twitter. What Are the Symptoms of a Heart Attack? Not all heart attacks begin with the sudden, ... This Content: NEXT >> Featured Video What is a heart attack? 05/22/2014 Describes how a heart attack ...

  17. Attack Coverage in High-Level Men’s Volleyball: Organization on the Edge of Chaos?

    Directory of Open Access Journals (Sweden)

    Laporta Lorenzo

    2015-09-01

    Full Text Available Change is pervasive, but emerging patterns are occasionally detectable through analysis of systemic behaviors. Match analysis uses these patterns in order to reduce the degree of improvisation and to optimize the training process. However, it is possible that certain game phases elude systematic patterning. In this vein, our aim was to analyze the case of attack coverage in men’s volleyball, as we suspected it would elude systematic patterning and has received negligible attention in scientific research. We analyzed the occurrence of attack coverage in 4544 plays of the 2011 Volleyball World League. A Chi-square test with residual adjusted values was applied to explore significant associations between variables. A Monte Carlo correction was applied, as some cells had n<5. Effect sizes were determined using Cramer’s V. Overall, attack coverage occurred in 3.89% of ball possessions, and 23 distinct structures emerged. These structures lacked significant associations with the game complex, setting zone, and effect of attack coverage. Conversely, attack coverage structures showed significant associations with the attack zone and tempo, with very strong effect sizes (V=0.472 and V=0.521, respectively. As certain attack zones are deeply associated with attack tempo, it is apparent that quicker attack plays affect attack coverage structuring, promoting the formation of less complex structures. Ultimately, attack coverage structures seem to depend on momentary constraints, thereby rendering rigid systematization impracticable. Still, we contended that a principle-based approach might be suitable. This invites researchers to rethink how to interpret game regularities.

  18. To mitigate Black-hole attack with CBDS in MANET

    OpenAIRE

    Navjot; Er.Pooja Ran

    2015-01-01

    Mobile ad-hoc network is self configured network that consist of mobile nodes which communicate with each other. Distributed self-organized nature of this network makes it venerable to various attacks likes DOS attack, Black hole attack, wormhole attack and jamming attack etc. Blackhole attack is one of the serious attack in network in which information loss occur which degrades the performance of network. In this work black hole attack is detected with the help of CBDS (cooperati...

  19. [Hereditary angioedema. Treatment of acute attacks in Argentina].

    Science.gov (United States)

    Malbrán, Alejandro; Malbrán, Eloisa; Menéndez, Alejandra; Fernández Romero, Diego S

    2014-01-01

    In the world, hereditary angioedema (HAE) affects 1 every 50000 persons. It is characterized by highly disabling and recurrent episodes of cutaneous, abdominal and laryngeal episodes of angioedema. Asphyxia related mortality ranges from 15 to 50%. In Argentina a plasma derived C1 inhibitor concentrate (pdC1INH) has been available for the treatment of acute attacks for many decades, however, only15 (26%) out of 58 patients had received pdC1INH at least once until 2008, and only2 (3.4%) had used it regularly. After worldwide approval of the new drugs for the treatment of acute HAE attacks, adding icatibant to pdC1INH in Argentina, and after publication of the therapeutic guide for the country, 42 (82%) out of 51 patients from the original group has pdC1INH available to treat their next attack. However, 16 (18%) patients continue without access to medication and other 15 (35.7%) obtain their therapy spuriously through some other affected relative in their environment. Only 12 (28.6%) patients of the group self-treated at home. Access to treatment has greatly improved, but needs to be extended to all patients and self-treatment at home should be encouraged.

  20. Shoulder injuries from attacking motion

    Science.gov (United States)

    Yanagi, Shigeru; Nishimura, Tetsu; Itoh, Masaru; Wada, Yuhei; Watanabe, Naoki

    1997-03-01

    Sports injuries have bothered professional players. Although many medical doctors try to treat injured players, to prevent sports injuries is more important. Hence, it is required to clear a kinematic mechanism of the sport injuries. A shoulder of volleyball attacker or baseball pitcher is often inured by playing motion. The injuries are mainly caused at the end of long head tendon, which is located in the upper side of scapula. Generally, a muscle and tendon have enough strength against tensile force, however, it seems that they are sometimes defeated by the lateral force. It is imagined that the effect of the lateral force has a possibility of injuring the tendon. If we find the influence of the lateral force on the injured portion, the mechanism of injuries must be cleared. In our research, volleyball attacking motion is taken by high speed video cameras. We analyze the motion as links system and obtain an acceleration of an arm and a shoulder from video image data. The generated force at a shoulder joint is calculated and resolved into the lateral and longitudinal forces. Our final goal is to discuss a possibility that the lateral force causes the injuries.

  1. Anger attacks in obsessive compulsive disorder

    Directory of Open Access Journals (Sweden)

    Nitesh Prakash Painuly

    2011-01-01

    Full Text Available Background: Research on anger attacks has been mostly limited to depression, and only a few studies have focused on anger attacks in obsessive compulsive disorder. Materials and Methods: In a cross-sectional study all new obsessive compulsive disorder patients aged 20-60 years attending an outpatient clinic were assessed using the anger attack questionnaire, irritability, depression and anxiety scale (for the direction of the aggressive behavior and quality of life (QOL. Results: The sample consisted of 42 consecutive subjects with obsessive compulsive disorder, out of which 21 (50% had anger attacks. The obsessive compulsive disorder subjects with and without anger attacks did not show significant differences in terms of sociodemographic variables, duration of illness, treatment, and family history. However, subjects with anger attacks had significantly higher prevalence of panic attacks and comorbid depression. Significantly more subjects with anger attacks exhibited aggressive acts toward spouse, parents, children, and other relatives in the form of yelling and threatening to hurt, trying to hurt, and threatening to leave. However, the two groups did not differ significantly in terms of QOL, except for the psychological domain being worse in the subjects with anger attacks. Conclusion: Anger attacks are present in half of the patients with obsessive compulsive disorder, and they correlate with the presence of comorbid depression.

  2. Corrosion inhibitor development for slightly sour environments with oxygen intrusion

    Energy Technology Data Exchange (ETDEWEB)

    Wylde, J.; Wang, H.; Li, J. [Clariant Oil Services North America, Calgary, AB (Canada)

    2009-07-01

    This presentation reported on a study that examined the effect of oxygen on the inhibition of carbon steel in slightly sour corrosion, and the initiation and propagation of localized attack. Oxygen can enter sour water injection systems through the vapor space in storage tanks and process system. Oxygen aggravates the corrosion attack by participating in the cathodic reaction under full or partial diffusion control. Laboratory testing results were reported in this presentation along with the development of corrosion inhibitors for such a slightly sour system. Bubble testing cells were used with continuous H{sub 2}/CO{sub 2} mixture gas sparging and occasional oxygen intrusion of 2 to 4 hours during a week long test. Linear polarization resistance (LPR) measurements and weight loss corrosion coupons were used to quantify the corrosion attack. The findings were presented in terms of the magnitude of localized attacks at different oxygen concentrations and intrusion periods, with and without the presence of corrosion inhibitors. tabs., figs.

  3. Attack Penetration System for SQL Injection

    Directory of Open Access Journals (Sweden)

    Manju Kaushik

    2014-06-01

    Full Text Available The SQL Injection attack is a popular way of attack in terms of document structure and common threats now a day. There are several ways of attack detection as per our study and also prevention methods had been discussed in several research papers. So the main motivation of our paper to penetrate the attack. For this we have proposed an efficient framework from which the central authority can control all the visited IP and restrict those IP. If the IP is in the restricted zone then the contents are restricted by using SQL update command with some status modification states. If the restricted IP wish to access the data from their credentials, it is immediately inform to the admin and the time of attack alert will be stored in the log area of that attack. Finally by comparison we will justify our results which are better in comparison to the previous test and methodology.

  4. Detection of Denial-of-service Attacks

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Denial-of-service (DOS) is a type of computer attack, which can essentially disable computers and networks.Resource consumption type of DOS attack could not be detected by the traditional misuse detection technique. This paper presents a new method of support vector mchine (SVM) to detect these attacks. We find that a DOS attack to a host is related to the activities within an impact data set of the host. The SVM method is used to classify the subsets of an impact data set to estimate its anomalism. The experiment result shows that this method can detect resource consumption type of DOS attacks, such as SYNflood, Smurf and UDP-storm. A receiver operating characteristic curve is plotted to determine performance for any possible operating point of the DOS attacks detection.

  5. FPGA Implementation of a Statistical Saturation Attack against PRESENT

    OpenAIRE

    Kerckhof, Stéphanie; Collard, Baudoin; Standaert, François-Xavier; AFRICACRYPT 2011

    2011-01-01

    Statistical attacks against block ciphers usually exploit “characteristics”. A characteristic essentially defines a relation between (parts of) the block cipher’s inputs, outputs and intermediate values. Intuitively, a good characteristic is one for which the relation between the cipher’s inputs and outputs exhibit a significant deviation from the uniform distribution. Due to its intensive computational complexity, the search for good characteristics generally relies on heuristics, e.g. based...

  6. Ancestry Analysis in the 11-M Madrid Bomb Attack Investigation

    OpenAIRE

    Christopher Phillips; Lourdes Prieto; Manuel Fondevila; Antonio Salas; Antonio Gómez-Tato; José Alvarez-Dios; Antonio Alonso; Alejandro Blanco-Verea; María Brión; Marta Montesino; Angel Carracedo; María Victoria Lareu

    2009-01-01

    The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a...

  7. Pediatric hereditary angioedema due to C1-inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.

  8. SQL INJECTION ATTACK DETECTION AND PREVENTION

    OpenAIRE

    Dr. SUNITHA ABBURU; PERUMALSAMY RAMASAMY

    2012-01-01

    Nowadays SQL injection attacks (SQLIAs) and cross scripting increased in real web applications very much, and the SQL injection attacks damages the databases through web applications. Injection queries are different type of way to attack the databases. This paper address the issue of SQLIA’s and script in an efficient way. The proposed approach detects and prevents all the Injection queries as well as the cross scripting through the Framework and Static analysis and Dynamic analysis. The cont...

  9. Fault Attack on the Balanced Shrinking Generator

    Institute of Scientific and Technical Information of China (English)

    GAO Juntao; LI Xuelian; HU Yupu

    2006-01-01

    Fault analysis, belonging to indirect attack, is a cryptanalysis technique for the physical implementation of cryptosystem. In this paper, we propose a fault attack on the Balanced Shrinking Generator. The results show that the attacker can obtain the secret key by analyzing faulty output sequences which is produced by changing control clock of one of Linear Feedback Shift Registers (LFSR). Therefore, the balanced shrinking generator has a trouble in hardware implementation.

  10. Ternary complex structures of human farnesyl pyrophosphate synthase bound with a novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme’s active site closure

    Directory of Open Access Journals (Sweden)

    Park Jaeok

    2012-12-01

    Full Text Available Abstract Background Human farnesyl pyrophosphate synthase (FPPS controls intracellular levels of farnesyl pyrophosphate, which is essential for various biological processes. Bisphosphonate inhibitors of human FPPS are valuable therapeutics for the treatment of bone-resorption disorders and have also demonstrated efficacy in multiple tumor types. Inhibition of human FPPS by bisphosphonates in vivo is thought to involve closing of the enzyme’s C-terminal tail induced by the binding of the second substrate isopentenyl pyrophosphate (IPP. This conformational change, which occurs through a yet unclear mechanism, seals off the enzyme’s active site from the solvent environment and is essential for catalysis. The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation. Results We have determined crystal structures of human FPPS in ternary complex with YS0470 and the secondary ligands inorganic phosphate (Pi, inorganic pyrophosphate (PPi, and IPP. Binding of PPi or IPP to the enzyme-inhibitor complex, but not that of Pi, resulted in full ordering of the C-terminal tail, which is most notably characterized by the anchoring of the R351 side chain to the main frame of the enzyme. Isothermal titration calorimetry experiments demonstrated that PPi binds more tightly to the enzyme-inhibitor complex than IPP, and differential scanning fluorometry experiments confirmed that Pi binding does not induce the tail ordering. Structure analysis identified a cascade of conformational changes required for the C-terminal tail rigidification involving Y349, F238, and Q242. The residues K57 and N59 upon PPi/IPP binding undergo subtler conformational changes, which may initiate this cascade. Conclusions In human FPPS, Y349 functions as a safety switch that prevents any futile C-terminal closure and is locked in the “off” position in the

  11. Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors

    OpenAIRE

    Larissa M. Podust; Poulos, Thomas L.; Waterman, Michael R.

    2001-01-01

    Cytochrome P450 14α-sterol demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes. CYP51 removes the 14α-methyl group from sterol precursors such as lanosterol, obtusifoliol, dihydrolanosterol, and 24(28)-methylene-24,25-dihydrolanosterol. Inhibitors of CYP51 include triazole antifungal agents fluconazole and itraconazole, drugs used in treatment of topical and systemic mycoses. The 2.1- and 2.2-Å crystal structures reported here for 4-phen...

  12. Abnormal brain processing of cutaneous pain in migraine patients during the attack.

    Science.gov (United States)

    de Tommaso, Marina; Guido, Marco; Libro, Giuseppe; Losito, Luciana; Sciruicchio, Vittorio; Monetti, Carlo; Puca, Francomichele

    2002-11-15

    We examined cutaneous pain thresholds using CO(2) laser stimuli during migraine attacks, and defined the evoked cortical potential characteristics. Ten patients without aura were studied during attacks and for at least 72 h subsequently. Pain stimuli were generated on the dorsum of both hands and the right and left supraorbital zones, using pulses from a CO(2) laser. Absolute latencies of scalp potentials were measured at the highest peak of each response component, and the peak-to-peak amplitudes of N2a-P2 components were recorded. Cutaneous pain thresholds were significantly reduced on both the symptomatic and non-symptomatic sides during the attack, in comparison with the headache-free phase. The N2a-P2 complexes also increased in amplitude during attacks in comparison with the pain-free side. Thus, cutaneous hyperalgesia occurs during migraine attack, and is subtended by central sensitization phenomena, probably involving the cortex.

  13. Where can an Insider attack?

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, René Rydhof; Nielson, Flemming

    2006-01-01

    the targeted organisation. While the problem is well recognised in the security community as well as in law-enforcement and intelligence communities, the main resort still is to audit log files \\$\\backslash\\$emph{after the fact}. There has been little research into developing models, automated tools......By definition, an insider has better access, is more trusted, and has better information about internal procedures, high-value targets, and potential weak spots in the security, than an outsider. Consequently, an insider attack has the potential to cause significant, even catastrophic, damage to...... properties of the modelled systems. Our analysis of processes identifies which actions may be performed by whom, at which locations, accessing which data. This allows to compute a superset of audit results---before an incident occurs....

  14. Evaluation of Hypervisor Stability towards Insider Attacks

    Institute of Scientific and Technical Information of China (English)

    Roman Kulikov; Svetlana Kolesnikova

    2016-01-01

    Virtualization technology plays a key role in cloud computing. Thus, the security issues of virtualization tools (hypervisors, emulators, etc.) should be under precise consideration. However, threats of insider attacks are underestimated. The virtualization tools and hypervisors have been poorly protected from this type of attacks. Furthermore, hypervisor is one of the most critical elements in cloud computing infrastructure. Firstly, hypervisor vulnerabilities analysis is provided. Secondly, a formal model of insider attack on hypervisor is developed. Consequently, on the basis of the formal attack model, we propose a new methodology of hypervisor stability evaluation. In this paper, certain security countermeasures are considered that should be integrated in hypervisor software architecture.

  15. Off-Path Attacking the Web

    CERN Document Server

    Gilad, Yossi

    2012-01-01

    We show how an off-path (spoofing-only) attacker can perform cross-site scripting (XSS), cross-site request forgery (CSRF) and site spoofing/defacement attacks, without requiring vulnerabilities in either web-browser or server and circumventing known defenses. Attacker can also launch devastating denial of service (DoS) attacks, even when the connection between the client and the server is secured with SSL/TLS. The attacks are practical and require a puppet (malicious script in browser sandbox) running on a the victim client machine, and attacker capable of IP-spoofing on the Internet. Our attacks use a technique allowing an off-path attacker to learn the sequence numbers of both client and server in a TCP connection. The technique exploits the fact that many computers, in particular those running Windows, use a global IP-ID counter, which provides a side channel allowing efficient exposure of the connection sequence numbers. We present results of experiments evaluating the learning technique and the attacks ...

  16. Hello Flood Attack and its Countermeasures in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Virendra Pal Singh

    2010-05-01

    Full Text Available Wireless sensor network have emerged as an important application of the ad-hoc networks paradigm, such as for monitoring physical environment. These sensor networks have limitations of system resources like battery power, communication range and processing capability. Low processing power and wireless connectivity make such networks vulnerable to various types of network attacks. One of them is hello flood attack, in which an adversary, which is not a legal node in the network, can flood hello request to any legitimate node and break the security of WSN. The current solutions for these types of attacks are mainly cryptographic, which suffer from heavy computational complexity. Hence they are less suitable for wireless sensor networks. In this paper a method based on signal strength has been proposed to detect and prevent hello flood attack. Nodes have been classified as friend and stranger based on the signal strength. Short client puzzles that require less computational power and battery power have been used to check the validity of suspicious nodes.

  17. Potential Security Attacks on Wireless Networks and their Countermeasure

    Directory of Open Access Journals (Sweden)

    Sreedhar. C

    2010-10-01

    Full Text Available The security of wireless networks has been a constant topic in the recent years. With the advance ofwireless networks, building reliable and secured communication is becoming extremely important.Wireless security is a mechanism of preventing unauthorized access or damage to computers usingwireless networks. A mobile ad-hoc network (MANET is a self-organizing system of mobile nodes thatcommunicate with each other through wireless links with no fixed infrastructure or centralizedadministration. This paper presents potential security attacks on Ad-hoc On-demand Distance Vector(AODV routing protocol and their countermeasure. IETF standardized AODV and considered as one ofthe most popular and promising on-demand routing protocols because of its lower network overhead andalgorithm complexity. AODV protocol does not store all the routing information in its routing table andthis causes potential security threat to the wireless networks. In this paper, we consider various knownsecurity attacks and in- specific blackhole attack on AODV and propose a countermeasure to thwartblackhole attack.

  18. Improved Collision Attack on Hash Function MD5

    Institute of Scientific and Technical Information of China (English)

    Jie Liang; Xue-Jia Lai

    2007-01-01

    In this paper, we present a fast attack algorithm to find two-block collision of hash function MD5.The algorithm is based on the two-block collision differential path of MD5 that was presented by Wang et al.In the Conference EUROCRYPT 2005.We found that the derived conditions for the desired collision differential path were not sufficient to guarantee the path to hold and that some conditions could be modified to enlarge the collision set.By using technique of small range searching and omitting the computing steps to check the characteristics in the attack algorithm, we can speed up the attack of MD5 efficiently.Compared with the Advanced Message Modification technique presented by Wang et al.,the small range searching technique can correct 4 more conditions for the first iteration differential and 3 more conditions for the second iteration differential, thus improving the probability and the complexity to find collisions.The whole attack on the MD5 can be accomplished within 5 hours using a PC with Pentium4 1.70GHz CPU.

  19. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik

    2016-08-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors.

  20. Development of an Attack-Resistant and Secure SCADA System using WSN, MANET, and Internet

    Directory of Open Access Journals (Sweden)

    N. Rajesh kumar

    2014-06-01

    Full Text Available Industrial Control Systems (ICS are open to security attacks when they are integrated with IT systems and wireless technologies for enhanced processing and remote control. These Critical Infrastructures (CIs are highly important as they provide service for an entire nation and causes serious danger even when interrupted for a while. Some of the common SCADA (Supervisory Control and Data Acquisition systems involve energy and water distribution systems. In this paper, the energy distribution SCADA system comprising several substations is considered. A secure framework is proposed that combines the energy control system with Wireless Sensor Networks (WSNs, Mobile Ad hoc Networks (MANETs, and the Internet, providing anomaly prevention and status management. SCADA attacks occur at the state estimators of the power systems which are used to route power flows and detect faulty devices. These estimators are located in the SCADA control center which is a sensitive area and measurements must be transmitted over a secure communication channel. The attack-resistance of the SCADA system is enhanced by increasing the hardness and complexity of the attack problem. The Attack-Resistant and Secure (ARS SCADA system is evaluated against existing techniques like NAMDIA (Network-Aware Mitigation of Data Integrity Attacks, Retrofit IDS (Intrusion Detection System, and CSBF (Critical State-Based Filtering for enhancing the attack-resistance and security of SCADA systems. It is found that the performance of ARS SCADA system is good compared to the existing methods in terms of maximum normalized attack impact and latency.

  1. Several novel N-donor tridentate ligands formed in chemical studies of new fac-Re(CO)3 complexes relevant to fac-99mTc(CO)3 radiopharmaceuticals: attack of a terminal amine on coordinated acetonitrile.

    Science.gov (United States)

    Perera, Theshini; Marzilli, Patricia A; Fronczek, Frank R; Marzilli, Luigi G

    2010-03-01

    To evaluate syntheses of fac-[Re(CO)(3)L](+) complexes in organic solvents, we treated fac-[Re(CO)(3)(CH(3)CN)(3)]PF(6)/BF(4) in acetonitrile with triamine ligands (L). When L had two primary or two tertiary terminal amine groups, the expected fac-[Re(CO)(3)L](+) complexes formed. In contrast, N,N-dimethyldiethylenetriamine (N,N-Me(2)dien) formed an unusual compound, fac-[Re(CO)(3)(DAE)]BF(4) {DAE = (Z)-N'-(2-(2-(dimethylamino)ethylamino)ethyl)acetimidamide = (Me(2)NCH(2)CH(2))NH(CH(2)CH(2)N=C(NH(2))Me)}. DAE is formed by addition of acetonitrile to the N,N-Me(2)dien terminal primary amine, converting this sp(3) nitrogen to an sp(2) nitrogen with a double bond to the original acetonitrile sp carbon. The three Ns bound to Re derive from N,N-Me(2)dien. The pathway to fac-[Re(CO)(3)(DAE)]BF(4) is suggested by a second unusual compound, fac-[Re(CO)(3)(MAE)]PF(6) {MAE = N-methyl-N-(2-(methyl-(2-(methylamino)ethyl)amino)ethyl)acetimidamide = MeN(H)-CH(2)CH(2)-N(Me)-CH(2)CH(2)-N(Me)-C(Me)=NH}, isolated after treating fac-[Re(CO)(3)(CH(3)CN)(3)]PF(6) with N,N',N''-trimethyldiethylenetriamine (N,N',N''-Me(3)dien). MAE chelates via a terminal and a central sp(3) N from N,N',N''-Me(3)dien and via one sp(2) NH in a C(Me)=NH group. This group is derived from acetonitrile by addition of the other N,N',N''-Me(3)dien terminal amine to the nitrile carbon. This addition creates an endocyclic NMe group within a seven-membered chelate ring. The structure and other properties of fac-[Re(CO)(3)(MAE)]PF(6) allow us to propose a reaction scheme for the formation of the unprecedented DAE ligand. The new compounds advance our understanding of the spectral and structural properties of Re analogues of (99m)Tc radiopharmaceuticals. PMID:20104873

  2. Optimal space-time attacks on system state estimation under a sparsity constraint

    Science.gov (United States)

    Lu, Jingyang; Niu, Ruixin; Han, Puxiao

    2016-05-01

    System state estimation in the presence of an adversary that injects false information into sensor readings has attracted much attention in wide application areas, such as target tracking with compromised sensors, secure monitoring of dynamic electric power systems, secure driverless cars, and radar tracking and detection in the presence of jammers. From a malicious adversary's perspective, the optimal strategy for attacking a multi-sensor dynamic system over sensors and over time is investigated. It is assumed that the system defender can perfectly detect the attacks and identify and remove sensor data once they are corrupted by false information injected by the adversary. With this in mind, the adversary's goal is to maximize the covariance matrix of the system state estimate by the end of attack period under a sparse attack constraint such that the adversary can only attack the system a few times over time and over sensors. The sparsity assumption is due to the adversary's limited resources and his/her intention to reduce the chance of being detected by the system defender. This becomes an integer programming problem and its optimal solution, the exhaustive search, is intractable with a prohibitive complexity, especially for a system with a large number of sensors and over a large number of time steps. Several suboptimal solutions, such as those based on greedy search and dynamic programming are proposed to find the attack strategies. Examples and numerical results are provided in order to illustrate the effectiveness and the reduced computational complexities of the proposed attack strategies.

  3. A Scalable Approach to Analyzing Network Security using Compact Attack Graphs

    Directory of Open Access Journals (Sweden)

    Feng Chen

    2010-05-01

    Full Text Available The compact attack graphs implicitly reveal the threat of sophisticated multi-step attacks by enumerating possible sequences of exploits leading to the compromising given critical resources in enterprise networks with thousands of hosts. For security analysts, the challenge is how to analyze the complex attack graphs with possible ten thousands of nodes for defending the security of network. In the paper, we will essentially discuss three issues about it. The first is to compute non-loop attack paths with the distance less than the given number that the real attacker may take practically in realistic attack scenarios. The second is how to measure security risk of the given critical resources.  The third is to find the solution to removing vulnerabilities in such a way that given critical resources cannot be compromised while the cost for such removal incurs the least cost. We propose the scalable approach to solve the above three issues respectively. The approach is proved to have a polynomial time complexity and can scale to the attack graphs with ten thousands of nodes corresponding large enterprise networks.

  4. The robustness of multiplex networks under layer node-based attack

    Science.gov (United States)

    Zhao, Da-Wei; Wang, Lian-Hai; Zhi, Yong-Feng; Zhang, Jun; Wang, Zhen

    2016-04-01

    From transportation networks to complex infrastructures, and to social and economic networks, a large variety of systems can be described in terms of multiplex networks formed by a set of nodes interacting through different network layers. Network robustness, as one of the most successful application areas of complex networks, has attracted great interest in a myriad of research realms. In this regard, how multiplex networks respond to potential attack is still an open issue. Here we study the robustness of multiplex networks under layer node-based random or targeted attack, which means that nodes just suffer attacks in a given layer yet no additional influence to their connections beyond this layer. A theoretical analysis framework is proposed to calculate the critical threshold and the size of giant component of multiplex networks when nodes are removed randomly or intentionally. Via numerous simulations, it is unveiled that the theoretical method can accurately predict the threshold and the size of giant component, irrespective of attack strategies. Moreover, we also compare the robustness of multiplex networks under multiplex node-based attack and layer node-based attack, and find that layer node-based attack makes multiplex networks more vulnerable, regardless of average degree and underlying topology.

  5. Preparation data of the bromodomains BRD3(1, BRD3(2, BRD4(1, and BRPF1B and crystallization of BRD4(1-inhibitor complexes

    Directory of Open Access Journals (Sweden)

    Martin Hügle

    2016-06-01

    Full Text Available This article presents detailed purification procedures for the bromodomains BRD3(1, BRD3(2, BRD4(1, and BRPF1B. In addition we provide crystallization protocols for apo BRD4(1 and BRD4(1 in complex with numerous inhibitors. The protocols described here were successfully applied to obtain affinity data by isothermal titration calorimetry (ITC and by differential scanning fluorimetry (DSF as well as structural characterizations of BRD4(1 inhibitor complexes (PDB codes: PDB: 4LYI, PDB: 4LZS, PDB: 4LYW, PDB: 4LZR, PDB: 4LYS, PDB: 5D24, PDB: 5D25, PDB: 5D26, PDB: 5D3H, PDB: 5D3J, PDB: 5D3L, PDB: 5D3N, PDB: 5D3P, PDB: 5D3R, PDB: 5D3S, PDB: 5D3T. These data have been reported previously and are discussed in more detail elsewhere [1,2].

  6. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  7. Automated Detection System for SQL Injection Attacks

    Directory of Open Access Journals (Sweden)

    Dr K.V.N.Sunitha

    2010-10-01

    Full Text Available Many software systems have evolved to include a Web-based component that makes them available to the public via the Internet and can expose them to a variety of Web-based attacks. One of these attacks is SQL Injection vulnerability (SQLIV, which can give attackers unrestricted access to the databases that underlie Web applications and has become increasingly frequent and serious. The intent is that Web applications will limit the kinds of queries that can be generated to a safe subset of all possible queries, regardless of what input users provide. SQL Injection attacks are possible due to the design drawbacks of the web sites, which interact with back-end databases. Successful attacks may damage more. We introduce a system that deals with new automated technique for preventing SQLIA based on the novel concept of regular expressions is to detect SQL Injection attacks. The proposed system can detect the attacks that are from Internet and Insider Attacks, by analyzing the packets of the network servers.

  8. Quantifying Shannon's work function for cryptanalytic attacks

    NARCIS (Netherlands)

    R.J.J.H. van Son

    2010-01-01

    Attacks on cryptographic systems are limited by the available computational resources. A theoretical understanding of these resource limitations is needed to evaluate the security of cryptographic primitives and procedures. This study uses an Attacker versus Environment game formalism based on compu

  9. Fast Collision Attack on MD5

    NARCIS (Netherlands)

    Stevens, M.M.J.

    2006-01-01

    In this paper, we present an improved attack algorithm to find two-block collisions of the hash function MD5. The attack uses the same differential path of MD5 and the set of sufficient conditions that was presented by Wang et al. We present a new technique which allows us to deterministically fulfi

  10. Internal differential collision attacks on the reduced-round Grøstl-0 hash function

    DEFF Research Database (Denmark)

    Ideguchi, Kota; Tischhauser, Elmar Wolfgang; Preneel, Bart

    2014-01-01

    . This results in collision attacks and semi-free-start collision attacks on the Grøstl-0 hash function and compression function with reduced rounds. Specifically, we show collision attacks on the Grøstl-0-256 hash function reduced to 5 and 6 out of 10 rounds with time complexities 248 and 2112 and on the Grøstl......-0-512 hash function reduced to 6 out of 14 rounds with time complexity 2183. Furthermore, we demonstrate semi-free-start collision attacks on the Grøstl-0-256 compression function reduced to 8 rounds and the Grøstl-0-512 compression function reduced to 9 rounds. Finally, we show improved...

  11. New Multi-step Worm Attack Model

    CERN Document Server

    Robiah, Y; Shahrin, S; Faizal, M A; Zaki, M Mohd; Marliza, R

    2010-01-01

    The traditional worms such as Blaster, Code Red, Slammer and Sasser, are still infecting vulnerable machines on the internet. They will remain as significant threats due to their fast spreading nature on the internet. Various traditional worms attack pattern has been analyzed from various logs at different OSI layers such as victim logs, attacker logs and IDS alert log. These worms attack pattern can be abstracted to form worms' attack model which describes the process of worms' infection. For the purpose of this paper, only Blaster variants were used during the experiment. This paper proposes a multi-step worm attack model which can be extended into research areas in alert correlation and computer forensic investigation.

  12. Combating Memory Corruption Attacks On Scada Devices

    Science.gov (United States)

    Bellettini, Carlo; Rrushi, Julian

    Memory corruption attacks on SCADA devices can cause significant disruptions to control systems and the industrial processes they operate. However, despite the presence of numerous memory corruption vulnerabilities, few, if any, techniques have been proposed for addressing the vulnerabilities or for combating memory corruption attacks. This paper describes a technique for defending against memory corruption attacks by enforcing logical boundaries between potentially hostile data and safe data in protected processes. The technique encrypts all input data using random keys; the encrypted data is stored in main memory and is decrypted according to the principle of least privilege just before it is processed by the CPU. The defensive technique affects the precision with which attackers can corrupt control data and pure data, protecting against code injection and arc injection attacks, and alleviating problems posed by the incomparability of mitigation techniques. An experimental evaluation involving the popular Modbus protocol demonstrates the feasibility and efficiency of the defensive technique.

  13. Automatic Classification of Attacks on IP Telephony

    Directory of Open Access Journals (Sweden)

    Jakub Safarik

    2013-01-01

    Full Text Available This article proposes an algorithm for automatic analysis of attack data in IP telephony network with a neural network. Data for the analysis is gathered from variable monitoring application running in the network. These monitoring systems are a typical part of nowadays network. Information from them is usually used after attack. It is possible to use an automatic classification of IP telephony attacks for nearly real-time classification and counter attack or mitigation of potential attacks. The classification use proposed neural network, and the article covers design of a neural network and its practical implementation. It contains also methods for neural network learning and data gathering functions from honeypot application.

  14. CompChall: Addressing Password Guessing Attacks

    CERN Document Server

    Goyal, Vipul; Singh, Mayank; Abraham, Ajith; Sanyal, Sugata

    2011-01-01

    Even though passwords are the most convenient means of authentication, they bring along themselves the threat of dictionary attacks. Dictionary attacks may be of two kinds: online and offline. While offline dictionary attacks are possible only if the adversary is able to collect data for a successful protocol execution by eavesdropping on the communication channel and can be successfully countered using public key cryptography, online dictionary attacks can be performed by anyone and there is no satisfactory solution to counter them. This paper presents a new authentication protocol which is called CompChall (computational challenge). The proposed protocol uses only one way hash functions as the building blocks and attempts to eliminate online dictionary attacks by implementing a challenge-response system. This challenge-response system is designed in a fashion that it does not pose any difficulty to a genuine user but is time consuming and computationally intensive for an adversary trying to launch a large n...

  15. SURVEY OF PACKET DROPPING ATTACK IN MANET

    Directory of Open Access Journals (Sweden)

    A.Janani

    2014-03-01

    Full Text Available Mobile Ad-hoc NETwork (MANET is an application of wireless network with self-configuring mobile nodes. MANET does not require any fixed infrastructure. Its development never has any threshold range. Nodes in MANET can communicate with each other if and only if all the nodes are in the same range. This wide distribution of nodes makes MANET vulnerable to various attacks, packet dropping attack or black hole attack is one of the possible attack. It is very hard to detect and prevent. To prevent from packet dropping attack, detection of misbehavior links and selfish nodes plays a vital role in MANETs. In this paper, a omprehensive investigation on detection of misbehavior links and malicious nodes is carried out.

  16. Use of Attack Graphs in Security Systems

    Directory of Open Access Journals (Sweden)

    Vivek Shandilya

    2014-01-01

    Full Text Available Attack graphs have been used to model the vulnerabilities of the systems and their potential exploits. The successful exploits leading to the partial/total failure of the systems are subject of keen security interest. Considerable effort has been expended in exhaustive modeling, analyses, detection, and mitigation of attacks. One prominent methodology involves constructing attack graphs of the pertinent system for analysis and response strategies. This not only gives the simplified representation of the system, but also allows prioritizing the security properties whose violations are of greater concern, for both detection and repair. We present a survey and critical study of state-of-the-art technologies in attack graph generation and use in security system. Based on our research, we identify the potential, challenges, and direction of the current research in using attack graphs.

  17. Evaluating Deterioration of Concrete by Sulfate Attack

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Effects of factors such as water to cement ratio, fly ash and silica fume on the resistance of concrete to sulfate attack were investigated by dry-wet cycles and immersion method. The index of the resistance to sulfate attack was used to evaluate the deterioration degree of concrete damaged by sulfate. The relationship between the resistance of concrete to sulfate attack and its permeability/porosity were analyzed as well as its responding mechanism. Results show that the depth of sulfate crystal attack from surface to inner of concrete can be reduced by decreasing w/c and addition of combining fly ash with silica fume. The variation of relative elastic modulus ratio and relative flexural strength ratio of various specimens before and after being subjected to sulfate attack was compared.

  18. Quantum attack-resistent certificateless multi-receiver signcryption scheme.

    Science.gov (United States)

    Li, Huixian; Chen, Xubao; Pang, Liaojun; Shi, Weisong

    2013-01-01

    The existing certificateless signcryption schemes were designed mainly based on the traditional public key cryptography, in which the security relies on the hard problems, such as factor decomposition and discrete logarithm. However, these problems will be easily solved by the quantum computing. So the existing certificateless signcryption schemes are vulnerable to the quantum attack. Multivariate public key cryptography (MPKC), which can resist the quantum attack, is one of the alternative solutions to guarantee the security of communications in the post-quantum age. Motivated by these concerns, we proposed a new construction of the certificateless multi-receiver signcryption scheme (CLMSC) based on MPKC. The new scheme inherits the security of MPKC, which can withstand the quantum attack. Multivariate quadratic polynomial operations, which have lower computation complexity than bilinear pairing operations, are employed in signcrypting a message for a certain number of receivers in our scheme. Security analysis shows that our scheme is a secure MPKC-based scheme. We proved its security under the hardness of the Multivariate Quadratic (MQ) problem and its unforgeability under the Isomorphism of Polynomials (IP) assumption in the random oracle model. The analysis results show that our scheme also has the security properties of non-repudiation, perfect forward secrecy, perfect backward secrecy and public verifiability. Compared with the existing schemes in terms of computation complexity and ciphertext length, our scheme is more efficient, which makes it suitable for terminals with low computation capacity like smart cards. PMID:23967037

  19. Quantum attack-resistent certificateless multi-receiver signcryption scheme.

    Directory of Open Access Journals (Sweden)

    Huixian Li

    Full Text Available The existing certificateless signcryption schemes were designed mainly based on the traditional public key cryptography, in which the security relies on the hard problems, such as factor decomposition and discrete logarithm. However, these problems will be easily solved by the quantum computing. So the existing certificateless signcryption schemes are vulnerable to the quantum attack. Multivariate public key cryptography (MPKC, which can resist the quantum attack, is one of the alternative solutions to guarantee the security of communications in the post-quantum age. Motivated by these concerns, we proposed a new construction of the certificateless multi-receiver signcryption scheme (CLMSC based on MPKC. The new scheme inherits the security of MPKC, which can withstand the quantum attack. Multivariate quadratic polynomial operations, which have lower computation complexity than bilinear pairing operations, are employed in signcrypting a message for a certain number of receivers in our scheme. Security analysis shows that our scheme is a secure MPKC-based scheme. We proved its security under the hardness of the Multivariate Quadratic (MQ problem and its unforgeability under the Isomorphism of Polynomials (IP assumption in the random oracle model. The analysis results show that our scheme also has the security properties of non-repudiation, perfect forward secrecy, perfect backward secrecy and public verifiability. Compared with the existing schemes in terms of computation complexity and ciphertext length, our scheme is more efficient, which makes it suitable for terminals with low computation capacity like smart cards.

  20. Detection Block Model for SQL Injection Attacks

    Directory of Open Access Journals (Sweden)

    Diksha G. Kumar

    2014-10-01

    Full Text Available With the rapid development of Internet, more and more organizations connect their databases to the Internet for resource sharing. However, due to developers' lack of knowledge of all possible attacks, web applications become vulnerable to multiple attacks. Thus the network databases could face multiple threats. Web applications generally consist of a three tier architecture where database is in the third pole, which is the most valuable asset in any organization. SQL injection is an attack technique in which specially crafted input string is entered in user input field. It is submitted to server and result is returned to the user. In SQL injection vulnerability, the database server is forced to execute malicious operations which may cause the data loss or corruption, denial of access, and unauthentic access to sensitive data by crafting specific inputs. An attacker can directly compromise the database, and that is why this is a most threatening web attack. SQL injection attack occupies first position in top ten vulnerabilities as specified by Open Web Application Security Project. It is probably the most common Website vulnerability today. Current scenarios which provide solutions to SQL injection attack either have limited scope i.e. can’t be implemented across all platforms, or do not cover all types of SQL injection attacks. In this work we implement Message Authentication Code (MAC based solution against SQL injection attacks. The model works both on client and server side. Client side implements a filter function and server side is based on information theory. MAC of static and dynamic queries is compared to detect SQL injection attack.

  1. Combining High-Level and Low-Level Approaches to Evaluate Software Implementations Robustness Against Multiple Fault Injection Attacks

    OpenAIRE

    Rivière, Lionel; Potet, Marie-Laure; Le, Thanh-Ha; Bringer, Julien; Chabanne, Hervé; Puys, Maxime

    2014-01-01

    International audience Physical fault injections break security functionalities of algorithms by targeting their implementations. Software techniques strengthen such implementations to enhance their robustness against fault attacks. Exhaustively testing physical fault injections is time consuming and requires complex platforms. Simulation solutions are developed for this specific purpose. We chose two independent tools presented in 2014, the Laser Attack Robustness (Lazart) and the Embedde...

  2. Research on First Attack Probability Model of an Attacker Level Bombing Anti-air Radars

    Institute of Scientific and Technical Information of China (English)

    LUO Peng-cheng; MU Fu-ling; ZHOU Jing-lun

    2007-01-01

    The paper mainly studies the first attack probability (FAP) of an attacker level bombing anti-air radars through analyzing the radiant point orientation and attack (RPOA) process of attackers. Firstly, the searching target process is analyzed, and a corresponding target finding model is brought forward. Secondly, the target approaching process is concretely analyzed when the attacker levelly bombs the anti-air radar, and a corresponding target approaching model is presented. Finally, a demonstration is given to analyze the major factors in the model and prove its validity.

  3. An Network Attack Modeling Method Based on MLL-AT

    Science.gov (United States)

    Fen, Yan; Xinchun, Yin; Hao, Huang

    In this paper, the method of modeling attack using attack tree is researched. The main goal is effectively using attack tree to model and express multi-stage network attacks. We expand and improve the traditional attack tree. The attack nodes in traditional attack tree are redefined, and the attack risk of leaf node is quantified. On those basis, the mentality and method of building MLL-AT (Multi-Level & Layer Attack Tree) are proposed. The improved attack tree can model attack more accurately, in particular to multi-stage network attacks. And the new model can also be used to evaluate system's risk, to distinguish between varying system security threat degrees caused by different attack sequences.

  4. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

    NARCIS (Netherlands)

    M. Levi; G. Choi; C. Picavet; C.E. Hack

    2006-01-01

    Background: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by Cl-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause co

  5. Robustness and structure of complex networks

    Science.gov (United States)

    Shao, Shuai

    This dissertation covers the two major parts of my PhD research on statistical physics and complex networks: i) modeling a new type of attack -- localized attack, and investigating robustness of complex networks under this type of attack; ii) discovering the clustering structure in complex networks and its influence on the robustness of coupled networks. Complex networks appear in every aspect of our daily life and are widely studied in Physics, Mathematics, Biology, and Computer Science. One important property of complex networks is their robustness under attacks, which depends crucially on the nature of attacks and the structure of the networks themselves. Previous studies have focused on two types of attack: random attack and targeted attack, which, however, are insufficient to describe many real-world damages. Here we propose a new type of attack -- localized attack, and study the robustness of complex networks under this type of attack, both analytically and via simulation. On the other hand, we also study the clustering structure in the network, and its influence on the robustness of a complex network system. In the first part, we propose a theoretical framework to study the robustness of complex networks under localized attack based on percolation theory and generating function method. We investigate the percolation properties, including the critical threshold of the phase transition pc and the size of the giant component Pinfinity. We compare localized attack with random attack and find that while random regular (RR) networks are more robust against localized attack, Erdoḧs-Renyi (ER) networks are equally robust under both types of attacks. As for scale-free (SF) networks, their robustness depends crucially on the degree exponent lambda. The simulation results show perfect agreement with theoretical predictions. We also test our model on two real-world networks: a peer-to-peer computer network and an airline network, and find that the real-world networks

  6. Utilizing Probabilistic Linear Equations in Cube Attacks

    Institute of Scientific and Technical Information of China (English)

    Yuan Yao; Bin Zhang; Wen-Ling Wu

    2016-01-01

    Cube attacks, proposed by Dinur and Shamir at EUROCRYPT 2009, have shown huge power against stream ciphers. In the original cube attacks, a linear system of secret key bits is exploited for key recovery attacks. However, we find a number of equations claimed linear in previous literature actually nonlinear and not fit into the theoretical framework of cube attacks. Moreover, cube attacks are hard to apply if linear equations are rare. Therefore, it is of significance to make use of probabilistic linear equations, namely nonlinear superpolys that can be approximated by linear expressions effectively. In this paper, we suggest a way to test out and utilize these probabilistic linear equations, thus extending cube attacks to a wider scope. Concretely, we employ the standard parameter estimation approach and the sequential probability ratio test (SPRT) for linearity test in the preprocessing phase, and use maximum likelihood decoding (MLD) for solving the probabilistic linear equations in the online phase. As an application, we exhibit our new attack against 672 rounds of Trivium and reduce the number of key bits to search by 7.

  7. Forensics Investigation of Web Application Security Attacks

    Directory of Open Access Journals (Sweden)

    Amor Lazzez

    2015-02-01

    Full Text Available Nowadays, web applications are popular targets for security attackers. Using specific security mechanisms, we can prevent or detect a security attack on a web application, but we cannot find out the criminal who has carried out the security attack. Being unable to trace back an attack, encourages hackers to launch new attacks on the same system. Web application forensics aims to trace back and attribute a web application security attack to its originator. This may significantly reduce the security attacks targeting a web application every day, and hence improve its security. The aim of this paper is to carry out a detailed overview about the web application forensics. First, we define the web applications forensics, and we present a taxonomic structure of the digital forensics. Then, we present the methodology of a web application forensics investigation. After that, we illustrate the forensics supportive tools for a web application forensics investigation. After that, we present a detailed presentation of a set of the main considered web application forensics tools. Finally, we provide a comparison of the main considered web application forensics tools.

  8. Adaptive cyber-attack modeling system

    Science.gov (United States)

    Gonsalves, Paul G.; Dougherty, Edward T.

    2006-05-01

    The pervasiveness of software and networked information systems is evident across a broad spectrum of business and government sectors. Such reliance provides an ample opportunity not only for the nefarious exploits of lone wolf computer hackers, but for more systematic software attacks from organized entities. Much effort and focus has been placed on preventing and ameliorating network and OS attacks, a concomitant emphasis is required to address protection of mission critical software. Typical software protection technique and methodology evaluation and verification and validation (V&V) involves the use of a team of subject matter experts (SMEs) to mimic potential attackers or hackers. This manpower intensive, time-consuming, and potentially cost-prohibitive approach is not amenable to performing the necessary multiple non-subjective analyses required to support quantifying software protection levels. To facilitate the evaluation and V&V of software protection solutions, we have designed and developed a prototype adaptive cyber attack modeling system. Our approach integrates an off-line mechanism for rapid construction of Bayesian belief network (BN) attack models with an on-line model instantiation, adaptation and knowledge acquisition scheme. Off-line model construction is supported via a knowledge elicitation approach for identifying key domain requirements and a process for translating these requirements into a library of BN-based cyber-attack models. On-line attack modeling and knowledge acquisition is supported via BN evidence propagation and model parameter learning.

  9. Smart Grid Integrity Attacks: Characterizations and Countermeasures

    Energy Technology Data Exchange (ETDEWEB)

    Annarita Giani; Eilyan Bitar; Miles McQueen; Pramod Khargonekar; Kameshwar Poolla

    2011-10-01

    Real power injections at loads and generators, and real power flows on selected lines in a transmission network are monitored, transmitted over a SCADA network to the system operator, and used in state estimation algorithms to make dispatch, re-balance and other energy management system [EMS] decisions. Coordinated cyber attacks of power meter readings can be arranged to be undetectable by any bad data detection algorithm. These unobservable attacks present a serious threat to grid operations. Of particular interest are sparse attacks that involve the compromise of a modest number of meter readings. An efficient algorithm to find all unobservable attacks [under standard DC load flow approximations] involving the compromise of exactly two power injection meters and an arbitrary number of power meters on lines is presented. This requires O(n2m) flops for a power system with n buses and m line meters. If all lines are metered, there exist canonical forms that characterize all 3, 4, and 5-sparse unobservable attacks. These can be quickly detected in power systems using standard graph algorithms. Known secure phase measurement units [PMUs] can be used as countermeasures against an arbitrary collection of cyber attacks. Finding the minimum number of necessary PMUs is NP-hard. It is shown that p + 1 PMUs at carefully chosen buses are sufficient to neutralize a collection of p cyber attacks.

  10. Rotational Rebound Attacks on Reduced Skein

    DEFF Research Database (Denmark)

    Khovratovich, Dmitry; Nikolic, Ivica; Rechberger, Christian

    2010-01-01

    In this paper we combine a recent rotational cryptanalysis with the rebound attack, which results in the best cryptanalysis of Skein, a candidate for the SHA-3 competition. The rebound attack approach was so far only applied to AES-like constructions. For the first time, we show that this approac...... inside-out computations and neutral bits in the inbound phase of the rebound attack, and give well-defined rotational distinguishers as certificates of weaknesses for the compression functions and block ciphers.......In this paper we combine a recent rotational cryptanalysis with the rebound attack, which results in the best cryptanalysis of Skein, a candidate for the SHA-3 competition. The rebound attack approach was so far only applied to AES-like constructions. For the first time, we show that this approach...... and the Threefish cipher. The new techniques include an analytical search for optimal input values in the rotational cryptanalysis, which allows to extend the outbound phase of the attack with a precomputation phase, an approach never used in any rebound-style attack before. Further we show how to combine multiple...

  11. Attack detection in unattended sensor networks

    Science.gov (United States)

    Wu, Curt; Monnier, Camille; Fry, Gerald; Girod, Lewis; Luke, Jahn

    2010-04-01

    Because sensor networks are often deployed in hostile environments where their security and integrity may be compromised, it is essential to maximize the reliability and trustworthiness of existing and envisioned sensor networks. During operations, the sensor network must be robust to deception, node compromise, and various other attacks, while maintaining the operator's situational awareness regarding the health and integrity of the system. To address these needs, we have designed a Framework to Ensure and Assess Trustworthiness in Sensor systems (FEATS) to identify attacks on sensor system integrity and inform the operator of sensor data trustworthiness. We have developed and validated unsupervised anomaly detection algorithms for sensor data captured from an experimental acoustic sensor platform under a number of attack scenarios. The platform, which contains four audio microphones, was exposed to two physical attacks (audio filtering and audio playback) as well as a live replay attack (replaying live audio data that is captured at a remote location), which is analogous to a wormhole attack in the routing layer. With our unsupervised learning algorithms, we were able to successfully identify the presence of various attacks.

  12. Attack graph generation method based on attack source excitation and attack atom filter%基于攻击源激发和攻击原子筛选的攻击图构建方法

    Institute of Scientific and Technical Information of China (English)

    焦波; 黄赪东; 黄飞; 李伟

    2013-01-01

    With the shortcoming of high time complexity and messy graphical presentation in large scale network application for attack graphs, this paper proposed a new generation method. The method visited network hosts using breadth-first traversing algorithm from attack sources based on target network model and attacker model, acquired attack atoms with attack patterns instantiation and confidential relationship for network connections between two hosts, filtered attack atoms through greedy principle and probability metric for attack atoms, and updated effect states of attack atoms. The experimental results show that the method can traverse once among hosts and filter attack atoms, not only has higher time efficiency, but also provides objective attack paths information for security events analyzing. The proposed method can meet the needs of attacking auxiliary decision, intrusion detection and network security evaluation in large scale network environment.%针对现有攻击图在大规模网络应用中存在的时间复杂性高和图形化展示凌乱等不足,提出一种新的构建方法:在目标网络模型和攻击者模型的基础上,以攻击源为起点广度遍历网络主机,针对主机间的网络连接,通过攻击模式实例化和信任关系获取攻击原子集,并根据攻击者贪婪原则和攻击原子发生概率计算尺度筛选攻击原子,同时更新攻击原子作用对象状态.通过实验分析,该方法面向网络主机实现一次遍历,筛选关键攻击原子,快速生成攻击图,不仅具有较高的时间效率,而且为安全事件分析提供客观的攻击路径信息.该方法能够满足大规模网络环境下的攻击辅助决策、入侵检测和网络安全评估等应用需求.

  13. Review Paper on Flooding Attack in MANET

    Directory of Open Access Journals (Sweden)

    Ruchita Meher,

    2014-01-01

    Full Text Available Mobile ad-hoc network (MANET is widely applicable in various areas like military services, civilian environments and emergency operations. The issues in MANET are broadcasting, clustering, mobility management, bandwidth management and power management. Broadcasting becomes an important issue in MANET for route information discovery. The different routing attacks in MANET are flooding, black hole, link spoofing and wormhole attack. In this paper we are representing works proposed by various author on flooding attack. Our contribution in this paper is that we have presented details comparison of various counter based schemes.

  14. Effect of Ergotamine on Headache and Migraine Attack Induced by Sindenafil Citrate

    OpenAIRE

    Rayka Sharifian; Ayoub Barzgarnejad; Fatemeh Ghanbarpour; Mehrdad Taghipour

    2015-01-01

    Sildenafil citrate is a potent vasodilatation agent to treat male erectile dysfunction and pulmonary hypertension. Among its adverse effects, headache and migraine attack have been widely reported. Here we focus on the effect of sildenafil, a selective inhibitor of CGMP hydrolyzing phosphodiesterase-5 (PDE-5), on headache induction. PDEs are large families of enzyme that break down cyclic nucleotides CGMP. When PDEs are inhibited, the levels of CGMP increase within vascular smooth muscle cell...

  15. Who Is at Risk for a Heart Attack?

    Science.gov (United States)

    ... on Twitter. Who Is at Risk for a Heart Attack? Certain risk factors make it more likely that ... This Content: NEXT >> Featured Video What is a heart attack? 05/22/2014 Describes how a heart attack ...

  16. Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

    2014-10-02

    Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

  17. Proposed Methodology for Securing Wireless LANs from Wormhole Attack

    OpenAIRE

    Patel, A K; Jaypalsinh. A. Gohil; D.T. Meva

    2010-01-01

    Wormhole attacks enable an attacker with limited Resources and no cryptographic material to wreak havoc on wireless networks. Initial research focused that this attack is possible only on Adhoc networks, but in present condition wormhole attack is possible on infrastructure based wireless LANs also. We propose architecture and analyze the possibility of wormhole attack along with a countermeasure to avoid such an attack. The proposed mechanism involves the shared information between commun...

  18. Password-only authenticated three-party key exchange proven secure against insider dictionary attacks.

    Science.gov (United States)

    Nam, Junghyun; Choo, Kim-Kwang Raymond; Paik, Juryon; Won, Dongho

    2014-01-01

    While a number of protocols for password-only authenticated key exchange (PAKE) in the 3-party setting have been proposed, it still remains a challenging task to prove the security of a 3-party PAKE protocol against insider dictionary attacks. To the best of our knowledge, there is no 3-party PAKE protocol that carries a formal proof, or even definition, of security against insider dictionary attacks. In this paper, we present the first 3-party PAKE protocol proven secure against both online and offline dictionary attacks as well as insider and outsider dictionary attacks. Our construct can be viewed as a protocol compiler that transforms any 2-party PAKE protocol into a 3-party PAKE protocol with 2 additional rounds of communication. We also present a simple and intuitive approach of formally modelling dictionary attacks in the password-only 3-party setting, which significantly reduces the complexity of proving the security of 3-party PAKE protocols against dictionary attacks. In addition, we investigate the security of the well-known 3-party PAKE protocol, called GPAKE, due to Abdalla et al. (2005, 2006), and demonstrate that the security of GPAKE against online dictionary attacks depends heavily on the composition of its two building blocks, namely a 2-party PAKE protocol and a 3-party key distribution protocol.

  19. 芳香酮曼尼希碱酸化缓蚀剂的合成及复配研究%Synthesis and complex of the corrosion inhibitor of mannich bases of aromatic ketones

    Institute of Scientific and Technical Information of China (English)

    王霞; 白媛丽; 罗全民; 刘志辉

    2012-01-01

    37% Formaldehyde solution,acetophenone and diethylamine were chosed ultimately and these materials compounded a new type of mannich base hydrochloride acid inhibitor, and its complex research. The results showed that the best synthetic process conditions is diethylamine, formaldehyde, acetophenone molar ratio is:2:2:1 .reaction time is 8 h,reaction temperature is 80℃,,reaction system pH value is 4. Sodi-um tungstate and corrosion inhibitor have a positive synergies, potassium iodide negative synergistic effect.%以37%的甲醛溶液、苯乙酮和二乙胺为原料,合成一种新型曼尼希碱盐酸酸化缓蚀剂,并对其进行复配研究.结果表明,最佳合成条件为:二乙胺、37%甲醛溶液和苯乙酮的摩尔比为2:2:1,反应时间8h,反应温度80 ℃,pH值为4;钨酸钠和缓蚀剂有着很好的正协同效应,碘化钾与其有负协同效应.

  20. 3-Nitropropionic Acid is a Suicide Inhibitor of MitochondrialRespiration that, Upon Oxidation by Complex II, Forms a Covalent AdductWith a Catalytic Base Arginine in the Active Site of the Enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-shar; Sun, Gang; Cobessi, David; Wang, Andy C.; Shen,John T.; Tung, Eric Y.; Anderson, Vernon E.; Berry, Edward A.

    2005-12-01

    We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. 1.3.5.1) at up to 2.1 {angstrom} resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg297 as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg297. The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg 297 to be increased by 83 Da and to have potential of losing 44 Da, consistent with decarboxylation, during fragmentation.

  1. 3-Nitropropionic Acid is a Suicide Inhibitor of Mitochondrial Respiration that, Upon Oxidation by Complex II, Forms a Covalent Adduct With a Catalytic Base Arginine in the Active Site of the Enzyme

    International Nuclear Information System (INIS)

    We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. 1.3.5.1) at up to 2.1 (angstrom) resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg297 as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg297. The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg 297 to be increased by 83 Da and to have potential of losing 44 Da, consistent with decarboxylation, during fragmentation

  2. SECURING MANET FROM BLACKHOLE AND WORMHOLE ATTACKS

    Directory of Open Access Journals (Sweden)

    C.M.Vidhyapathi

    2013-06-01

    Full Text Available Mobile Ad-Hoc networks are self-configuring and self-organizing multi-hop wireless networks. They do not have any fixed infrastructure or centralized management. Due to this, the ad hoc networks are vulnerable to attacks. The routing protocol for MANET considered in this paper is AODV(Ad hoc On-demand Distance Vector Routing Protocol. Blackhole and Wormhole nodes are malicious nodeswhich degrade the performance of the network. They actively participate in the network and conform to forward packets to the destination. The Watchdog Mechanism is used to correct the network from both blackhole and wormhole attacks. The networks originally, with the attacks and after being prevented from attacks are compared on the basis of packets received, throughput, end-to-end delay and packet delivery ratio. ns2 software is used for the simulation.

  3. SQL INJECTION ATTACK DETECTION AND PREVENTION

    Directory of Open Access Journals (Sweden)

    Dr. SUNITHA ABBURU

    2012-04-01

    Full Text Available Nowadays SQL injection attacks (SQLIAs and cross scripting increased in real web applications very much, and the SQL injection attacks damages the databases through web applications. Injection queries are different type of way to attack the databases. This paper address the issue of SQLIA’s and script in an efficient way. The proposed approach detects and prevents all the Injection queries as well as the cross scripting through the Framework and Static analysis and Dynamic analysis. The contribution is twofold 1. SQL Injection AttackDetection and prevention 2. SQL Injection Reports. These techniques have been implemented in ASP.Net and SQL Server and tested by conducting various experiments and prove that the web applications and database is protected from scripting and SQL injection queries.

  4. AN APPROACH OF DEFENDING AGAINST DDOS ATTACK

    Institute of Scientific and Technical Information of China (English)

    Wu Zhijun; Duan Haixin; Li Xing

    2006-01-01

    An approach of defending against Distributed Denial of Service (DDoS) attack based on flow model and flow detection is presented. The proposed approach can protect targets from DDoS attacking, and allow targets to provide good service to legitimate traffic under DDoS attacking, with fast reaction. This approach adopts the technique of dynamic comb filter, yields a low level of false positives of less than 1.5%,drops similar percentage of good traffic, about 1%, and passes neglectable percentage of attack bandwidth to the victim, less than 1.5%. The prototype of commercial product, D-fighter, is developed by implementing this proposed approach on Intel network processor platform IXP 1200.

  5. Recovery of infrastructure networks after localised attacks

    Science.gov (United States)

    Hu, Fuyu; Yeung, Chi Ho; Yang, Saini; Wang, Weiping; Zeng, An

    2016-04-01

    The stability of infrastructure network is always a critical issue studied by researchers in different fields. A lot of works have been devoted to reveal the robustness of the infrastructure networks against random and malicious attacks. However, real attack scenarios such as earthquakes and typhoons are instead localised attacks which are investigated only recently. Unlike previous studies, we examine in this paper the resilience of infrastructure networks by focusing on the recovery process from localised attacks. We introduce various preferential repair strategies and found that they facilitate and improve network recovery compared to that of random repairs, especially when population size is uneven at different locations. Moreover, our strategic repair methods show similar effectiveness as the greedy repair. The validations are conducted on simulated networks, and on real networks with real disasters. Our method is meaningful in practice as it can largely enhance network resilience and contribute to network risk reduction.

  6. Compiling symbolic attacks to protocol implementation tests

    Directory of Open Access Journals (Sweden)

    Michael Rusinowitch

    2013-07-01

    Full Text Available Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically generating abstract attacks and converting them to concrete tests on protocol implementations. In particular we aim to improve previously proposed blackbox testing methods in order to discover automatically new attacks and vulnerabilities. As a proof of concept we have experimented our proposed architecture to detect a renegotiation vulnerability on some implementations of SSL/TLS, a protocol widely used for securing electronic transactions.

  7. On localization attacks against cloud infrastructure

    Science.gov (United States)

    Ge, Linqiang; Yu, Wei; Sistani, Mohammad Ali

    2013-05-01

    One of the key characteristics of cloud computing is the device and location independence that enables the user to access systems regardless of their location. Because cloud computing is heavily based on sharing resource, it is vulnerable to cyber attacks. In this paper, we investigate a localization attack that enables the adversary to leverage central processing unit (CPU) resources to localize the physical location of server used by victims. By increasing and reducing CPU usage through the malicious virtual machine (VM), the response time from the victim VM will increase and decrease correspondingly. In this way, by embedding the probing signal into the CPU usage and correlating the same pattern in the response time from the victim VM, the adversary can find the location of victim VM. To determine attack accuracy, we investigate features in both the time and frequency domains. We conduct both theoretical and experimental study to demonstrate the effectiveness of such an attack.

  8. Diabetes - preventing heart attack and stroke

    Science.gov (United States)

    Diabetes complications - heart; Coronary artery disease - diabetes; CAD - diabetes; Cerebrovascular disease - diabetes ... People with diabetes have a higher chance of having heart attacks and strokes. Smoking and having high blood pressure and high ...

  9. The role of sleep in migraine attacks

    Directory of Open Access Journals (Sweden)

    Elaine Inamorato

    1993-11-01

    Full Text Available Migraine attacks may be precipitated by sleep deprivation or excessive sleep and sleep is also associated with relief of migraine attacks. In view of this variable relationship we studied the records of 159 consecutive outpatients of our Headache Unit. In 121 records there was reference to sleep involvement, in 55% by a single form and in 45% by more than one form. When only one form was related, relief was most common (70%. 30% of that group of patients had the migraine attack precipitated by sleep, 24% by deprivation and 6% by sleep excess. When the effects of sleep were multiple, these effects were as expected logically in 65%: «in accordance» group (e.g attack precipitated by sleep deprivation and relieved by sleep onset. In a second group, («conflicting» where the involvement was not logical, there were three different combinations of sleep involvement, possibly due to more than one pathophysiological mechanism.

  10. Twisted Polynomials and Forgery Attacks on GCM

    DEFF Research Database (Denmark)

    Abdelraheem, Mohamed Ahmed A. M. A.; Beelen, Peter; Bogdanov, Andrey;

    2015-01-01

    nonce misuse resistance, such as POET. The algebraic structure of polynomial hashing has given rise to security concerns: At CRYPTO 2008, Handschuh and Preneel describe key recovery attacks, and at FSE 2013, Procter and Cid provide a comprehensive framework for forgery attacks. Both approaches rely...... heavily on the ability to construct forgery polynomials having disjoint sets of roots, with many roots (“weak keys”) each. Constructing such polynomials beyond naïve approaches is crucial for these attacks, but still an open problem. In this paper, we comprehensively address this issue. We propose to use...... in an improved key recovery algorithm. As cryptanalytic applications of our twisted polynomials, we develop the first universal forgery attacks on GCM in the weak-key model that do not require nonce reuse. Moreover, we present universal weak-key forgeries for the nonce-misuse resistant AE scheme POET, which...

  11. Karachi Commander Escapes Attack, 10 Dead

    Institute of Scientific and Technical Information of China (English)

    潘志强

    2004-01-01

    KARACHI: The army commander in the Pakistani city of Karachi narrowly① escaped assassination② yesterday when gunmen attacked his convoy③ with gunfire and a bomb, killing at least 10 and wounding his driver, officials said.

  12. Prevention of Routing Attacks In Manet

    Directory of Open Access Journals (Sweden)

    N.Rajesh

    2013-01-01

    Full Text Available Mobile Ad hoc Networks (MANET are easily prone to attacks due to its network infrastructure. In previous routing attacks the malicious node is isolated using naive fuzzy response decisions. In this paper a new technology of broadcasting the awareness information about attacker node to all the existing nodes in the network is discussed. The awareness approach is based on an extended Dempster-Shafer mathematical theory(D-S Theory. Dempster-Shafer mathematical theory is used to collect the evidence notion of importance factors. The adaptiveness of the mechanism allows to systematically cope with the identified MANET routing attacks. The intrusion response action in MANET was addressed by isolating uncooperative nodes based on the node reputation derived from their behaviors. Here the effectiveness of the approach with the consideration of the packet delivery ratio and routing cost were demonstrated using java swing concepts

  13. Thatcher condemns attacks on abortion mp.

    Science.gov (United States)

    1987-12-19

    The Prime Minister, Mrs Margaret Thatcher, has stepped in to condemn a series of violent attacks on Liberal MP David Alton who is trying to reduce the [Illegible word] limit on abortions from 28 to 18 weeks.

  14. To mitigate Black-hole attack with CBDS in MANET

    Directory of Open Access Journals (Sweden)

    Navjot

    2015-06-01

    Full Text Available Mobile ad-hoc network is self configured network that consist of mobile nodes which communicate with each other. Distributed self-organized nature of this network makes it venerable to various attacks likes DOS attack, Black hole attack, wormhole attack and jamming attack etc. Blackhole attack is one of the serious attack in network in which information loss occur which degrades the performance of network. In this work black hole attack is detected with the help of CBDS (cooperative Bait Detection Algorithm and MD5 is used for the security purpose. This work is implemented in Network simulator and performance is checked on the bases of network parameters.

  15. CASE STUDY OF SQL INJECTION ATTACKS

    OpenAIRE

    Sonakshi*, Rakesh Kumar, Girdhar Gopal

    2016-01-01

    Today, most of the web applications are associated with database at back-end so there are possibilities of SQL injection attacks (SQLIA) on it. A number of preventive measures have also been discovered by various researchers to overcome this attack, but which measure is more convenient and provides fast access to application without compromising the security is also a major concern nowadays. This paper provides a clear distinction among different types of SQLIAs and how these can be performed...

  16. Textual Manipulation for SQL Injection Attacks

    OpenAIRE

    Hussein AlNabulsi; Izzat Alsmadi; Mohammad Al-Jarrah

    2013-01-01

    SQL injection attacks try to use string or text manipulations to access illegally websites and their databases. This is since using some symbols or characters in SQL statements may trick the authentication system to incorrectly allow such SQL statements to be processed or executed. In this paper, we highlighted several examples of such text manipulations that can be successfully used in SQL injection attacks. We evaluated the usage of those strings on several websites and web pages using SNOR...

  17. Panic Attack during Elective Gastrointestinal Endoscopy

    OpenAIRE

    Charalampos Mitsonis; Nikolaos Dimopoulos; Marianna Zavrou; Vassiliki Psarra; Christos Giofkos; Christos Fiorakis; Athanasios Dimitriadis; Dimitrios Valavanis; Eleni Vousoura; Iannis Zervas; Efstathios Papavassiliou

    2011-01-01

    Background. Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) can evoke anxiety, embarrassment, and discomfort. These concerns can culminate in panic attacks, which may traumatize patients and significantly decrease their compliance to the procedure. The objective of this study was to evaluate the relationship between preendoscopic anxiety and the possibility of a panic attack during an elective gastrointestinal endoscopy (EGE). Methods. The study population comprised of 79 Greek outpatie...

  18. Compiling symbolic attacks to protocol implementation tests

    OpenAIRE

    Michael Rusinowitch; Ghazi Maatoug; Hatem Ghabri

    2013-01-01

    Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically g...

  19. Cyber Security Audit and Attack Detection Toolkit

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Dale

    2012-05-31

    This goal of this project was to develop cyber security audit and attack detection tools for industrial control systems (ICS). Digital Bond developed and released a tool named Bandolier that audits ICS components commonly used in the energy sector against an optimal security configuration. The Portaledge Project developed a capability for the PI Historian, the most widely used Historian in the energy sector, to aggregate security events and detect cyber attacks.

  20. Two Improved Multiple-Differential Collision Attacks

    OpenAIRE

    An Wang; Liji Wu; Zongyue Wang; Xuexin Zheng; Man Chen; Jing Ma

    2014-01-01

    In CHES 2008, Bogdanov proposed multiple-differential collision attacks which could be applied to the power analysis attacks on practical cryptographic systems. However, due to the effect of countermeasures on FPGA, there are some difficulties during the collision detection, such as local high noise and the lack of sampling points. In this paper, keypoints voting test is proposed for solving these problems, which can increase the success ratio from 35% to 95% on the example of one implementat...

  1. Logical Modes of Attack in Argumentation Networks

    OpenAIRE

    Gabbay, Dov M.; Garcez, A. S. D. Avila

    2009-01-01

    This paper studies methodologically robust options for giving logical contents to nodes in abstract argumentation networks. It defines a variety of notions of attack in terms of the logical contents of the nodes in a network. General properties of logics are refined both in the object level and in the meta level to suit the needs of the application. The network-based system improves upon some of the attempts in the literature to define attacks in terms of defeasible proofs, the...

  2. Copper(II) complexes with highly water-soluble L- and D-proline-thiosemicarbazone conjugates as potential inhibitors of Topoisomerase IIα.

    Science.gov (United States)

    Bacher, Felix; Enyedy, Éva A; Nagy, Nóra V; Rockenbauer, Antal; Bognár, Gabriella M; Trondl, Robert; Novak, Maria S; Klapproth, Erik; Kiss, Tamás; Arion, Vladimir B

    2013-08-01

    Two proline-thiosemicarbazone bioconjugates with excellent aqueous solubility, namely, 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone [L-Pro-FTSC or (S)-H2L] and 3-methyl-(R)-pyrrolidine-2-carboxylate-2-formylpyridine thiosemicarbazone [D-Pro-FTSC or (R)-H2L], have been synthesized and characterized by elemental analysis, one- and two-dimensional (1)H and (13)C NMR spectroscopy, and electrospray ionization mass spectrometry. The complexation behavior of L-Pro-FTSC with copper(II) in an aqueous solution and in a 30% (w/w) dimethyl sulfoxide/water mixture has been studied via pH potentiometry, UV-vis spectrophotometry, electron paramagnetic resonance, (1)H NMR spectroscopy, and spectrofluorimetry. By the reaction of copper(II) acetate with (S)-H2L and (R)-H2L in water, the complexes [Cu(S,R)-L] and [Cu(R,S)-L] have been synthesized and comprehensively characterized. An X-ray diffraction study of [Cu(S,R)-L] showed the formation of a square-pyramidal complex, with the bioconjugate acting as a pentadentate ligand. Both copper(II) complexes displayed antiproliferative activity in CH1 ovarian carcinoma cells and inhibited Topoisomerase IIα activity in a DNA plasmid relaxation assay. PMID:23829568

  3. Distinguishing attack and second-preimage attack on encrypted message authentication codes (EMAC)

    Science.gov (United States)

    Ariwibowo, Sigit; Windarta, Susila

    2016-02-01

    In this paper we show that distinguisher on CBC-MAC can be applied to Encrypted Message Authentication Code (EMAC) scheme. EMAC scheme in general is vulnerable to distinguishing attack and second preimage attack. Distinguishing attack simulation on AES-EMAC using 225 message modifications, no collision have been found. According to second preimage attack simulation on AES-EMAC no collision found between EMAC value of S1 and S2, i.e. no second preimage found for messages that have been tested. Based on distinguishing attack simulation on truncated AES-EMAC we found collision in every message therefore we cannot distinguish truncated AES-EMAC with random function. Second-preimage attack is successfully performed on truncated AES-EMAC.

  4. Identifying optimal targets of network attack by belief propagation

    Science.gov (United States)

    Mugisha, Salomon; Zhou, Hai-Jun

    2016-07-01

    For a network formed by nodes and undirected links between pairs of nodes, the network optimal attack problem aims at deleting a minimum number of target nodes to break the network down into many small components. This problem is intrinsically related to the feedback vertex set problem that was successfully tackled by spin-glass theory and an associated belief propagation-guided decimation (BPD) algorithm [Zhou, Eur. Phys. J. B 86, 455 (2013), 10.1140/epjb/e2013-40690-1]. In the present work we apply the BPD algorithm (which has approximately linear time complexity) to the network optimal attack problem and demonstrate that it has much better performance than a recently proposed collective information algorithm [Morone and Makse, Nature 524, 65 (2015), 10.1038/nature14604] for different types of random networks and real-world network instances. The BPD-guided attack scheme often induces an abrupt collapse of the whole network, which may make it very difficult to defend.

  5. High angle of attack aerodynamics subsonic, transonic, and supersonic flows

    CERN Document Server

    Rom, Josef

    1992-01-01

    The aerodynamics of aircraft at high angles of attack is a subject which is being pursued diligently, because the modern agile fighter aircraft and many of the current generation of missiles must perform well at very high incidence, near and beyond stall. However, a comprehensive presentation of the methods and results applicable to the studies of the complex aerodynamics at high angle of attack has not been covered in monographs or textbooks. This book is not the usual textbook in that it goes beyond just presenting the basic theoretical and experimental know-how, since it contains reference material to practical calculation methods and technical and experimental results which can be useful to the practicing aerospace engineers and scientists. It can certainly be used as a text and reference book for graduate courses on subjects related to high angles of attack aerodynamics and for topics related to three-dimensional separation in viscous flow courses. In addition, the book is addressed to the aerodynamicist...

  6. Monitoring of sulphate attack on hardened cement paste studied by synchrotron XRD

    Science.gov (United States)

    Stroh, J.; Meng, B.; Emmerling, F.

    2015-10-01

    The complex matter of external sulphate attack on cement-based construction materials is still not completely understood. The concentration of sulphate is a crucial factor for the formation of secondary phases and phase transitions of cement hydrates due to sulphate ingress into the microstructure. The sulphate attack on building materials for high and low sulphate concentrations was monitored by laboratory experiments. Hardened cement paste consisting of ordinary Portland cement (CEM I) were exposed to aqueous solutions of sodium sulphate for 18 months. Three sample compositions were used for this research, including different supplementary cementitious materials (SCM). The phase composition was determined for different time spans by high resolution synchrotron X-ray diffraction. Cross sections of exposed cement prisms were investigated as a representation of the microstructural profile. Based on the data, a temporal and spatial determination of the stages of the sulphate attack and the deterioration course was possible. Cement matrices blended with slag showed the highest resistance against sulphate attack.

  7. Zero-correlation linear cryptanalysis with FFT and improved attacks on ISO standards Camellia and CLEFIA

    DEFF Research Database (Denmark)

    Bogdanov, Andrey; Geng, Huizheng; Wang, Meiqin;

    2014-01-01

    Zero-correlation linear cryptanalysis is based on the linear approximations with correlation exactly zero, which essentially generalizes the integral property, and has already been applied to several block ciphers - among others, yielding best known attacks to date on round-reduced TEA and CAST-256....... Namely, we present zero-correlation attacks on 11-round Camellia-128 and 12-round Camellia-192 with FL/FL-1 and whitening key starting from the first round, which is an improvement in the number of attacked rounds in both cases. Moreover, we provide multidimensional zero-correlation cryptanalysis of 14......-round CLEFIA-192 and 15-round CLEFIA-256 that are attacks on the highest numbers of rounds in the classical single-key setting, respectively, with improvements in memory complexity. © 2014 Springer-Verlag....

  8. Blocking of SQL Injection Attacks by Comparing Static and Dynamic Queries

    Directory of Open Access Journals (Sweden)

    Raman Kumar

    2013-02-01

    Full Text Available Due to internet expansion web applications have now become a part of everyday life. As a result a number of incidents which exploit web application vulnerabilities are increasing. A large number of these incidents are SQL Injection attacks which are a serious security threat to databases which contain sensitive information, the leakage of which cause a large amount of loss. SQL Injection Attacks occur when an intruder changes the query structure by inserting any malicious input. There are a number of methods available to detect and prevent SQL Injection Attacks. But these are too complex to use. This paper proposes a very simple, effective and time saving technique to detect SQLIAs which uses combined static and dynamic analysis and also defines an attack other than existing classification of SQLIAs.

  9. The resilience of interdependent transportation networks under targeted attack

    CERN Document Server

    Zhang, Peng; Zhao, Zhuang; Li, Daqing; Lu, Guangquan; Wang, Yunpeng; Xiao, Jinghua

    2013-01-01

    Modern world builds on the resilience of interdependent infrastructures characterized as complex networks. Recently, a framework for analysis of interdependent networks has been developed to explain the mechanism of resilience in interdependent networks. Here we extend this interdependent network model by considering flows in the networks and study the system's resilience under different attack strategies. In our model, nodes may fail due to either overload or loss of interdependency. Under the interaction between these two failure mechanisms, it is shown that interdependent scale-free networks show extreme vulnerability. The resilience of interdependent SF networks is found in our simulation much smaller than single SF network or interdependent SF networks without flows.

  10. Pathologic features of fatal shark attacks.

    Science.gov (United States)

    Byard, R W; Gilbert, J D; Brown, K

    2000-09-01

    To examine the pattern of injuries in cases of fatal shark attack in South Australian waters, the authors examined the files of their institution for all cases of shark attack in which full autopsies had been performed over the past 25 years, from 1974 to 1998. Of the seven deaths attributed to shark attack during this period, full autopsies were performed in only two cases. In the remaining five cases, bodies either had not been found or were incomplete. Case 1 was a 27-year-old male surfer who had been attacked by a shark. At autopsy, the main areas of injury involved the right thigh, which displayed characteristic teeth marks, extensive soft tissue damage, and incision of the femoral artery. There were also incised wounds of the right wrist. Bony injury was minimal, and no shark teeth were recovered. Case 2 was a 26-year-old male diver who had been attacked by a shark. At autopsy, the main areas of injury involved the left thigh and lower leg, which displayed characteristic teeth marks, extensive soft tissue damage, and incised wounds of the femoral artery and vein. There was also soft tissue trauma to the left wrist, with transection of the radial artery and vein. Bony injury was minimal, and no shark teeth were recovered. In both cases, death resulted from exsanguination following a similar pattern of soft tissue and vascular damage to a leg and arm. This type of injury is in keeping with predator attack from underneath or behind, with the most severe injuries involving one leg. Less severe injuries to the arms may have occurred during the ensuing struggle. Reconstruction of the damaged limb in case 2 by sewing together skin, soft tissue, and muscle bundles not only revealed that no soft tissue was missing but also gave a clearer picture of the pattern of teeth marks, direction of the attack, and species of predator.

  11. New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers in Cancer Cells

    Science.gov (United States)

    Padhye, Subhash; Yang, Huanjie; Jamadar, Abeda; Cui, Qiuzhi Cindy; Chavan, Deepak; Dominiak, Kristin; McKinney, Jaclyn; Banerjee, Sanjeev; Dou, Q. Ping; Sarkar, Fazlul H.

    2013-01-01

    Purpose Emerging evidence clearly suggests the potential chemopreventive and anti-tumor activity of a well known “natural agent” curcumin. However, studies have shown that curcumin is not readily bioavailable, and thus the tissue bioavailability of curcumin is also poor except for gastrointestinal track. Because of the potential biological activity of curcumin, many studies have attempted for making a better analog of cucumin that is equally effective or better with increased bioavailability, which was the purpose of our current study. Methods We have designed and synthesized new difluoro Knoevenagel condensates of curcumin and Schiff bases along with their copper (II) complexes and evaluated their biological activities with respect to the inhibitory effects on purified rabbit 26S proteasome, and growth inhibition and induction of apoptosis in colon and pancreatic cancer cell lines. Results All copper complexes possess distorted square planar geometries with 1:1 metal to ligand stoichiometry with reversible copper redox couple. The difluoro compound CDF exhibited inhibitory effects on purified rabbit 20S proteasome or cellular 26S proteasome, and caused both growth inhibition of cancer cell lines and induced apoptotic cell death in our preliminary assessment. Conclusion Our results suggest that our newly synthesized classes of curcumin analogs could be useful as chemopreventive and/or therapeutic agents against cancers. PMID:19421843

  12. Power analysis attacks revealing the secrets of smart cards

    CERN Document Server

    Mangard, Stefan; Popp, Thomas

    2008-01-01

    A comprehensive treatment of power analysis attacks and countermeasures. Based on the principle that the only way to defend against power analysis attacks is to understand them, this book explains how power analysis attacks work. It discusses simple and differential power analysis as well as advanced techniques like template attacks.

  13. Coronary Artery Dissection: Not Just a Heart Attack

    Science.gov (United States)

    ... Stroke More Coronary Artery Dissection: Not Just a Heart Attack Updated:May 24,2016 Sometimes a heart attack ... Disease Go Red For Women Types of aneurysms Heart Attack • Home • About Heart Attacks Acute Coronary Syndrome (ACS) • ...

  14. A Game Theoretic Approach to Cyber Attack Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Peng Liu

    2005-11-28

    The area investigated by this project is cyber attack prediction. With a focus on correlation-based prediction, current attack prediction methodologies overlook the strategic nature of cyber attack-defense scenarios. As a result, current cyber attack prediction methodologies are very limited in predicting strategic behaviors of attackers in enforcing nontrivial cyber attacks such as DDoS attacks, and may result in low accuracy in correlation-based predictions. This project develops a game theoretic framework for cyber attack prediction, where an automatic game-theory-based attack prediction method is proposed. Being able to quantitatively predict the likelihood of (sequences of) attack actions, our attack prediction methodology can predict fine-grained strategic behaviors of attackers and may greatly improve the accuracy of correlation-based prediction. To our best knowledge, this project develops the first comprehensive framework for incentive-based modeling and inference of attack intent, objectives, and strategies; and this project develops the first method that can predict fine-grained strategic behaviors of attackers. The significance of this research and the benefit to the public can be demonstrated to certain extent by (a) the severe threat of cyber attacks to the critical infrastructures of the nation, including many infrastructures overseen by the Department of Energy, (b) the importance of cyber security to critical infrastructure protection, and (c) the importance of cyber attack prediction to achieving cyber security.

  15. Performance Evaluation of AODV with Blackhole Attack

    Science.gov (United States)

    Dara, Karuna

    2010-11-01

    A Mobile Ad Hoc Network (MANET) is a temporary network set up by a wireless mobile computers moving arbitrary in the places that have no network infrastructure. These nodes maintain connectivity in a decentralized manner. Since the nodes communicate with each other, they cooperate by forwarding data packets to other nodes in the network. Thus the nodes find a path to the destination node using routing protocols. However, due to security vulnerabilities of the routing protocols, mobile ad-hoc networks are unprotected to attacks of the malicious nodes. One of these attacks is the Black Hole Attack against network integrity absorbing all data packets in the network. Since the data packets do not reach the destination node on account of this attack, data loss will occur. In this paper, we simulated the black hole attack in various mobile ad-hoc network scenarios using AODV routing protocol of MANET and have tried to find a effect if number of nodes are increased with increase in malicious nodes.

  16. Panic Attack during Elective Gastrointestinal Endoscopy

    Directory of Open Access Journals (Sweden)

    Charalampos Mitsonis

    2011-01-01

    Full Text Available Background. Esophagogastroduodenoscopy (EGD and colonoscopy (CS can evoke anxiety, embarrassment, and discomfort. These concerns can culminate in panic attacks, which may traumatize patients and significantly decrease their compliance to the procedure. The objective of this study was to evaluate the relationship between preendoscopic anxiety and the possibility of a panic attack during an elective gastrointestinal endoscopy (EGE. Methods. The study population comprised of 79 Greek outpatients. The examination was carried out without the use of conscious sedation. Patients' anxiety levels were assessed before the procedure using the Greek version of the Spielberger State-Trait Anxiety Inventory (STAI-Y. Results. Seventy-nine patients were enrolled: 45 EGD and 34 CS. Females had higher state and trait anxiety levels than males (48.14 ± 7.94 versus 44.17 ± 7.43, <0.05; and 43.68 ± 6.95 versus 39.86 ± 7.46, <0.05. Patients who experienced panic attack had significantly higher levels of both trait and state anxiety, compared to those who were panic-free. There was no significant relationship between panic attacks and sex or type of procedure. Conclusions. Patients who experience panic attacks during endoscopic procedures appear to have significantly higher anxiety levels before the procedure. Administering the STAI questionnaire prior to the endoscopy seems to be a useful screening method for vulnerable patients.

  17. Modeling attacking of high skills volleyball players

    Directory of Open Access Journals (Sweden)

    Vladimir Gamaliy

    2014-12-01

    Full Text Available Purpose: to determine the model indicators of technical and tactical actions in the attack highly skilled volleyball players. Material and Methods: the study used statistical data of major international competitions: Olympic Games – 2012 World Championships – 2010, World League – 2010–2014 European Championship – 2010–2014. A total of 130 analyzed games. Methods were used: analysis and generalization of scientific and methodological literature, analysis of competitive activity highly skilled volleyball players, teacher observation, modeling technical and tactical actions in attacking highly skilled volleyball players. Results: it was found that the largest volume application of technical and tactical actions in the attack belongs to the group tactics «supple movement», whose indicator is 21,3%. The smallest amount of application belongs to the group tactics «flight level» model whose indicators is 5,4%, the efficiency of 3,4%, respectively. It is found that the power service in the jump from model parameters used in 51,6% of cases, the planning targets – 21,7% and 4,4% planning to reduce. Attacks performed with the back line, on model parameters used in the amount of 20,8% efficiency –13,7%. Conclusions: we prove that the performance of technical and tactical actions in the attack can be used as model in the control system of training and competitive process highly skilled volleyball players

  18. Panic Attack during Elective Gastrointestinal Endoscopy.

    Science.gov (United States)

    Mitsonis, Charalampos; Dimopoulos, Nikolaos; Zavrou, Marianna; Psarra, Vassiliki; Giofkos, Christos; Fiorakis, Christos; Dimitriadis, Athanasios; Valavanis, Dimitrios; Vousoura, Eleni; Zervas, Iannis; Papavassiliou, Efstathios

    2011-01-01

    Background. Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) can evoke anxiety, embarrassment, and discomfort. These concerns can culminate in panic attacks, which may traumatize patients and significantly decrease their compliance to the procedure. The objective of this study was to evaluate the relationship between preendoscopic anxiety and the possibility of a panic attack during an elective gastrointestinal endoscopy (EGE). Methods. The study population comprised of 79 Greek outpatients. The examination was carried out without the use of conscious sedation. Patients' anxiety levels were assessed before the procedure using the Greek version of the Spielberger State-Trait Anxiety Inventory (STAI-Y). Results. Seventy-nine patients were enrolled: 45 EGD and 34 CS. Females had higher state and trait anxiety levels than males (48.14 ± 7.94 versus 44.17 ± 7.43, P < 0.05; and 43.68 ± 6.95 versus 39.86 ± 7.46, P < 0.05). Patients who experienced panic attack had significantly higher levels of both trait and state anxiety, compared to those who were panic-free. There was no significant relationship between panic attacks and sex or type of procedure. Conclusions. Patients who experience panic attacks during endoscopic procedures appear to have significantly higher anxiety levels before the procedure. Administering the STAI questionnaire prior to the endoscopy seems to be a useful screening method for vulnerable patients. PMID:22007196

  19. Detecting and Localizing Wireless Network Attacks Techniques

    Directory of Open Access Journals (Sweden)

    Iyad Aldasouqi

    2010-03-01

    Full Text Available In order to increase employee productivity within a feasible budget, we have to track newtechnologies, investigate and choose the best plan and implementation of these technologies.WLAN is vulnerable to malicious attacks due to their shared medium in unlicensed frequencyspectrum, thus requiring security features for a variety of applications.This paper will discuss some techniques and approaches which can help to detect, localize andidentify wireless network attacks, which present a unique set of challenges to IT and securityprofessionals. All efforts were focusing on the ability to identity based attacks in which amalicious device uses forged MAC addresses to masquerade as a specific client or to createmultiple illegitimate identities. Also, to be sure that the network is able to robustly identify eachtransmitter independently of packet contents, allowing detection of a large class of identity-basedattacks with high probability.The attacker can listen to all wireless traffic, compromise encryption and Use attenuators,amplifiers, directional antennas, software radios, but he cannot be at the location of user or at thelocation of access points. However, we have to choose the best design, implementation, andevaluation techniques in order to secure our network from attackers, where our choice willdepend on a technical implementation to mitigate the risk on the enterprise network infrastructure.

  20. Proposed Methodology for Securing Wireless LANs from Wormhole Attack

    Directory of Open Access Journals (Sweden)

    A.K. Patel

    2010-05-01

    Full Text Available Wormhole attacks enable an attacker with limited Resources and no cryptographic material to wreak havoc on wireless networks. Initial research focused that this attack is possible only on Adhoc networks, but in present condition wormhole attack is possible on infrastructure based wireless LANs also. We propose architecture and analyze the possibility of wormhole attack along with a countermeasure to avoid such an attack. The proposed mechanism involves the shared information between communicating Access Points to prevent Rouge Access Points from masquerading as false neighbours. Our defense greatly diminishes the threat of wormhole attacks and requires no location information or clock synchronization.

  1. Attack Prevention for Collaborative Spectrum Sensing in Cognitive Radio Networks

    CERN Document Server

    Duan, Lingjie; Huang, Jianwei; Shin, Kang G

    2011-01-01

    Collaborative spectrum sensing can significantly improve the detection performance of secondary unlicensed users (SUs). However, the performance of collaborative sensing is vulnerable to sensing data falsification attacks, where malicious SUs (attackers) submit manipulated sensing reports to mislead the fusion center's decision on spectrum occupancy. Moreover, attackers may not follow the fusion center's decision regarding their spectrum access. This paper considers a challenging attack scenario where multiple rational attackers overhear all honest SUs' sensing reports and cooperatively maximize attackers' aggregate spectrum utilization. We show that, without attack-prevention mechanisms, honest SUs are unable to transmit over the licensed spectrum, and they may further be penalized by the primary user for collisions due to attackers' aggressive transmissions. To prevent such attacks, we propose two novel attack-prevention mechanisms with direct and indirect punishments. The key idea is to identify collisions...

  2. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I

    International Nuclear Information System (INIS)

    The activation of the transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor development, tumor progression, and resistance to chemo- and radiotherapy. In order to identify compounds targeting the HIF pathway, a small molecule library was screened using a luciferase-driven HIF-1 reporter cell line under hypoxia. The high-throughput screening led to the identification of a class of aminoalkyl-substituted compounds that inhibited hypoxia-induced HIF-1 target gene expression in human lung cancer cell lines at low nanomolar concentrations. Lead structure BAY 87-2243 was found to inhibit HIF-1α and HIF-2α protein accumulation under hypoxic conditions in non-small cell lung cancer (NSCLC) cell line H460 but had no effect on HIF-1α protein levels induced by the hypoxia mimetics desferrioxamine or cobalt chloride. BAY 87-2243 had no effect on HIF target gene expression levels in RCC4 cells lacking Von Hippel–Lindau (VHL) activity nor did the compound affect the activity of HIF prolyl hydroxylase-2. Antitumor activity of BAY 87-2243, suppression of HIF-1α protein levels, and reduction of HIF-1 target gene expression in vivo were demonstrated in a H460 xenograft model. BAY 87-2243 did not inhibit cell proliferation under standard conditions. However under glucose depletion, a condition favoring mitochondrial ATP generation as energy source, BAY 87-2243 inhibited cell proliferation in the nanomolar range. Further experiments revealed that BAY 87-2243 inhibits mitochondrial complex I activity but has no effect on complex III activity. Interference with mitochondrial function to reduce hypoxia-induced HIF-1 activity in tumors might be an interesting therapeutic approach to overcome chemo- and radiotherapy-resistance of hypoxic tumors

  3. A Traceability Attack against e-Passports

    Science.gov (United States)

    Chothia, Tom; Smirnov, Vitaliy

    Since 2004, many nations have started issuing "e-passports" containing an RFID tag that, when powered, broadcasts information. It is claimed that these passports are more secure and that our data will be protected from any possible unauthorised attempts to read it. In this paper we show that there is a flaw in one of the passport's protocols that makes it possible to trace the movements of a particular passport, without having to break the passport's cryptographic key. All an attacker has to do is to record one session between the passport and a legitimate reader, then by replaying a particular message, the attacker can distinguish that passport from any other. We have implemented our attack and tested it successfully against passports issued by a range of nations.

  4. Early Detection of SQL Injection Attacks

    Directory of Open Access Journals (Sweden)

    Hossain Shahriar

    2013-07-01

    Full Text Available SQL Injection (SQLI is a common vulnerability found in web applications.The starting point of SQLIattack is the client-side (browser. If attack inputs can be detected early at the browse side, then it could bethwarted early by not forwarding the malicious inputs to the server-side for further processing.This paperpresents a client-side approach to detect SQLI attacks1. The client-side accepts shadow SQL queries fromthe server-side and checks any deviation betweenshadow queries with dynamic queries generated withuser supplied inputs. We measure the deviation of shadow query and dynamic query based on conditionalentropy metrics and propose four metrics in this direction. We evaluate the approach with three PHPapplications containing SQLI vulnerabilities. The evaluation results indicate that our approach can detectwell-known SQLI attacks early at the client-side and impose negligible overhead.

  5. Quantifying Mixed Uncertainties in Cyber Attacker Payoffs

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Samrat; Halappanavar, Mahantesh; Tipireddy, Ramakrishna; Oster, Matthew R.; Saha, Sudip

    2015-04-15

    Representation and propagation of uncertainty in cyber attacker payoffs is a key aspect of security games. Past research has primarily focused on representing the defender’s beliefs about attacker payoffs as point utility estimates. More recently, within the physical security domain, attacker payoff uncertainties have been represented as Uniform and Gaussian probability distributions, and intervals. Within cyber-settings, continuous probability distributions may still be appropriate for addressing statistical (aleatory) uncertainties where the defender may assume that the attacker’s payoffs differ over time. However, systematic (epistemic) uncertainties may exist, where the defender may not have sufficient knowledge or there is insufficient information about the attacker’s payoff generation mechanism. Such epistemic uncertainties are more suitably represented as probability boxes with intervals. In this study, we explore the mathematical treatment of such mixed payoff uncertainties.

  6. Attacker Modelling in Ubiquitous Computing Systems

    DEFF Research Database (Denmark)

    Papini, Davide

    , localisation services and many others. These technologies can be classified under the name of ubiquitous systems. The term Ubiquitous System dates back to 1991 when Mark Weiser at Xerox PARC Lab first referred to it in writing. He envisioned a future where computing technologies would have been melted...... in with our everyday life. This future is visible to everyone nowadays: terms like smartphone, cloud, sensor, network etc. are widely known and used in our everyday life. But what about the security of such systems. Ubiquitous computing devices can be limited in terms of energy, computing power and memory...... attacker remain somehow undened and still under extensive investigation. This Thesis explores the nature of the ubiquitous attacker with a focus on how she interacts with the physical world and it denes a model that captures the abilities of the attacker. Furthermore a quantitative implementation...

  7. A taxonomy and discussion of software attack technologies

    Science.gov (United States)

    Banks, Sheila B.; Stytz, Martin R.

    2005-03-01

    Software is a complex thing. It is not an engineering artifact that springs forth from a design by simply following software coding rules; creativity and the human element are at the heart of the process. Software development is part science, part art, and part craft. Design, architecture, and coding are equally important activities and in each of these activities, errors may be introduced that lead to security vulnerabilities. Therefore, inevitably, errors enter into the code. Some of these errors are discovered during testing; however, some are not. The best way to find security errors, whether they are introduced as part of the architecture development effort or coding effort, is to automate the security testing process to the maximum extent possible and add this class of tools to the tools available, which aids in the compilation process, testing, test analysis, and software distribution. Recent technological advances, improvements in computer-generated forces (CGFs), and results in research in information assurance and software protection indicate that we can build a semi-intelligent software security testing tool. However, before we can undertake the security testing automation effort, we must understand the scope of the required testing, the security failures that need to be uncovered during testing, and the characteristics of the failures. Therefore, we undertook the research reported in the paper, which is the development of a taxonomy and a discussion of software attacks generated from the point of view of the security tester with the goal of using the taxonomy to guide the development of the knowledge base for the automated security testing tool. The representation for attacks and threat cases yielded by this research captures the strategies, tactics, and other considerations that come into play during the planning and execution of attacks upon application software. The paper is organized as follows. Section one contains an introduction to our research

  8. Quantifying Public Response towards Islam on Twitter after Paris Attacks

    OpenAIRE

    Magdy, Walid; Darwish, Kareem; Abokhodair, Norah

    2015-01-01

    The Paris terrorist attacks occurred on November 13, 2015 prompted a massive response on social media including Twitter, with millions of posted tweets in the first few hours after the attacks. Most of the tweets were condemning the attacks and showing support to Parisians. One of the trending debates related to the attacks concerned possible association between terrorism and Islam and Muslims in general. This created a global discussion between those attacking and those defending Islam and M...

  9. Defeating pharming attacks at the client-side

    OpenAIRE

    Gastellier-Prevost, Sophie; LAURENT, Maryline

    2011-01-01

    International audience With the deployment of "always-connected" broadband Internet access, personal networks are a privileged target for attackers and DNS-based corruption. Pharming attacks - an enhanced version of phishing attacks - aim to steal users' credentials by redirecting them to a fraudulent login website, using DNS-based techniques that make the attack imperceptible to the end-user. In this paper, we define an advanced approach to alert the end-user in case of pharming attacks a...

  10. Discovering Collaborative Cyber Attack Patterns Using Social Network Analysis

    Science.gov (United States)

    Du, Haitao; Yang, Shanchieh Jay

    This paper investigates collaborative cyber attacks based on social network analysis. An Attack Social Graph (ASG) is defined to represent cyber attacks on the Internet. Features are extracted from ASGs to analyze collaborative patterns. We use principle component analysis to reduce the feature space, and hierarchical clustering to group attack sources that exhibit similar behavior. Experiments with real world data illustrate that our framework can effectively reduce from large dataset to clusters of attack sources exhibiting critical collaborative patterns.

  11. Resistance of the double random phase encryption against various attacks.

    Science.gov (United States)

    Frauel, Yann; Castro, Albertina; Naughton, Thomas J; Javidi, Bahram

    2007-08-01

    Several attacks are proposed against the double random phase encryption scheme. These attacks are demonstrated on computer-generated ciphered images. The scheme is shown to be resistant against brute force attacks but susceptible to chosen and known plaintext attacks. In particular, we describe a technique to recover the exact keys with only two known plain images. We compare this technique to other attacks proposed in the literature.

  12. Mortality and management of 96 shark attacks and development of a shark bite severity scoring system.

    Science.gov (United States)

    Lentz, Ashley K; Burgess, George H; Perrin, Karen; Brown, Jennifer A; Mozingo, David W; Lottenberg, Lawrence

    2010-01-01

    Humans share a fascination and fear of sharks. We predict that most shark attacks are nonfatal but require skilled, timely medical intervention. The development of a shark bite severity scoring scale will assist communication and understanding of such an injury. We retrospectively reviewed records of the prospectively maintained International Shark Attack File (ISAF) at the University of Florida. The ISAF contains 4409 investigations, including 2979 documented attacks, 96 of which have complete medical records. We developed a Shark-Induced Trauma (SIT) Scale and calculated the level of injury for each attack. Medical records were reviewed for the 96 documented shark attack victims since 1921. Calculated levels of injury in the SIT Scale reveal 40 Level 1 injuries (41.7%), 16 Level 2 injuries (16.7%), 18 Level 3 injuries (18.8%), 14 Level 4 injuries (14.6%), and eight Level 5 injuries (8.3%). The overall mortality of shark attacks was 8.3 per cent. However, SIT Scale Level 1 injuries comprised the greatest percentage of cases at 41.7 per cent. Injury to major vascular structures increases mortality and necessitates immediate medical attention and definitive care by a surgeon. Shark bites deserve recognition with prompt resuscitation, washout, débridement, and follow up for prevention of infection and closure of more complex wounds.

  13. Playing Attack and Defense with Trusted Storage

    DEFF Research Database (Denmark)

    Gonzalez, Javier; Bonnet, Philippe; Bouganim, Luc

    2014-01-01

    It is often convenient to assume in a data management platform that one or several computing devices are trusted, specially when the goal is to provide privacy guarantees over personal data. But what does it take for a computing device to be trusted? More specifically, how can a personal device...... provide trusted storage? This is the question we tackle in this demonstration. We describe how secure devices, equipped with a trusted execution environment, differ from general purpose devices. We illustrate with our demonstration scenario, that it is much more difficult to attack a storage service...... running on a secure device, than to attack the same service running on a general purpose device....

  14. Defending Against Wormhole Attack in OLSR

    Institute of Scientific and Technical Information of China (English)

    HONG Liang; HONG Fan; FU Cai

    2006-01-01

    OLSR (optimal link state routing) is one of the four basic routing protocols used in mobile ad hoc Networks by the MANET working group of IETF(Internet engineering task force). OLSR, a proactive routing protocol, is based on a multipoint relaying flooding technique to reduce the number of topology broadcast. OLSR uses periodic HELLO packets to neighbor detection. As introduced in Reference [1], the wormhole attack can form a serious threat in wireless Networks, especially against many ad hoc Network routing protocols and location-based wireless security systems. Here, a trust model to handle this attack in OLSR is provided and simulated in NS2.

  15. Textual Manipulation for SQL Injection Attacks

    Directory of Open Access Journals (Sweden)

    Hussein AlNabulsi

    2013-11-01

    Full Text Available SQL injection attacks try to use string or text manipulations to access illegally websites and their databases. This is since using some symbols or characters in SQL statements may trick the authentication system to incorrectly allow such SQL statements to be processed or executed. In this paper, we highlighted several examples of such text manipulations that can be successfully used in SQL injection attacks. We evaluated the usage of those strings on several websites and web pages using SNORT open source. We also conducted an extensive comparison study of some relevant papers.

  16. Session Initiation Protocol Attacks and Challenges

    CERN Document Server

    Keshavarz, Hassan; Noor, Rafidah Md

    2012-01-01

    In recent years, Session Initiation Protocol (SIP) has become widely used in current internet protocols. It is a text-based protocol much like Hyper Text Transport Protocol (HTTP) and Simple Mail Transport Protocol (SMTP). SIP is a strong enough signaling protocol on the internet for establishing, maintaining, and terminating session. In this paper the areas of security and attacks in SIP are discussed. We consider attacks from diverse related perspectives. The authentication schemes are compared, the representative existing solutions are highlighted, and several remaining research challenges are identified. Finally, the taxonomy of SIP threat will be presented.

  17. Fast Collision Attack on MD5

    OpenAIRE

    Stevens, Marc

    2006-01-01

    In this paper, we present an improved attack algorithm to find two-block collisions of the hash function MD5. The attack uses the same differential path of MD5 and the set of sufficient conditions that was presented by Wang et al. We present a new technique which allows us to deterministically fulfill restrictions to properly rotate the differentials in the first round. We will present a new algorithm to find the first block and we will use an algorithm of Klima to find the second block. To o...

  18. HDAC Inhibitors.

    Science.gov (United States)

    Olzscha, Heidi; Bekheet, Mina E; Sheikh, Semira; La Thangue, Nicholas B

    2016-01-01

    Lysine acetylation in proteins is one of the most abundant posttranslational modifications in eukaryotic cells. The dynamic homeostasis of lysine acetylation and deacetylation is dictated by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). Important substrates for HATs and HDACs are histones, where lysine acetylation generally leads to an open and transcriptionally active chromatin conformation. Histone deacetylation forces the compaction of the chromatin with subsequent inhibition of transcription and reduced gene expression. Unbalanced HAT and HDAC activity, and therefore aberrant histone acetylation, has been shown to be involved in tumorigenesis and progression of malignancy in different types of cancer. Therefore, the development of HDAC inhibitors (HDIs) as therapeutic agents against cancer is of great interest. However, treatment with HDIs can also affect the acetylation status of many other non-histone proteins which play a role in different pathways including angiogenesis, cell cycle progression, autophagy and apoptosis. These effects have led HDIs to become anticancer agents, which can initiate apoptosis in tumor cells. Hematological malignancies in particular are responsive to HDIs, and four HDIs have already been approved as anticancer agents. There is a strong interest in finding adequate biomarkers to predict the response to HDI treatment. This chapter provides information on how to assess HDAC activity in vitro and determine the potency of HDIs on different HDACs. It also gives information on how to analyze cellular markers following HDI treatment and to analyze tissue biopsies from HDI-treated patients. Finally, a protocol is provided on how to detect HDI sensitivity determinants in human cells, based on a pRetroSuper shRNA screen upon HDI treatment. PMID:27246222

  19. Managing burn victims of suicide bombing attacks: outcomes, lessons learnt, and changes made from three attacks in Indonesia

    OpenAIRE

    Chim, Harvey; Yew, Woon Si; Song, Colin

    2007-01-01

    Introduction Terror attacks in Southeast Asia were almost nonexistent until the 2002 Bali bomb blast, considered the deadliest attack in Indonesian history. Further attacks in 2003 (Jakarta), 2004 (Jakarta), and 2005 (Bali) have turned terrorist attacks into an ever-present reality. Methods The authors reviewed medical charts of victims evacuated to the Singapore General Hospital (SGH) Burns Centre during three suicide attacks involving Bali (2002 and 2005) and the Jakarta Marriott hotel (200...

  20. Cinnoline derivatives as human neutrophil elastase inhibitors.

    Science.gov (United States)

    Giovannoni, Maria Paola; Schepetkin, Igor A; Crocetti, Letizia; Ciciani, Giovanna; Cilibrizzi, Agostino; Guerrini, Gabriella; Khlebnikov, Andrei I; Quinn, Mark T; Vergelli, Claudia

    2016-08-01

    Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195. PMID:26194018

  1. Combination of the histone deacetylase inhibitor depsipeptide and 5-fluorouracil upregulates major histocompatibility complex class II and p21 genes and activates caspase-3/7 in human colon cancer HCT-116 cells.

    Science.gov (United States)

    Okada, Kouji; Hakata, Shuko; Terashima, Jun; Gamou, Toshie; Habano, Wataru; Ozawa, Shogo

    2016-10-01

    Epigenetic anticancer drugs such as histone deacetylase (HDAC) inhibitors have been combined with existing anticancer drugs for synergistic or additive effects. In the present study, we found that a very low concentration of depsipeptide, an HDAC inhibitor, potentiated the antitumor activity of 5-fluorouracil (5-FU) in a human colon cancer cell model using HCT-116, HT29, and SW48 cells via the inhibition of colony formation ability or cellular viability. Exposure to a combination of 5-FU (1.75 µM) and 1 nM depsipeptide for 24 and 48 h resulted in a 3- to 4-fold increase in activated caspase-3/7, while 5-FU alone failed to activate caspase-3/7. Microarray and subsequent gene ontology analyses revealed that compared to 5-FU or depsipeptide alone, the combination treatment of 5-FU and depsipeptide upregulated genes related to cell death and the apoptotic process consistent with the inhibition of colony formation and caspase-3/7 activation. These analyses indicated marked upregulation of antigen processing and presentation of peptide or polysaccharide antigen via major histocompatibility complex (MHC) class (GO:0002504) and MHC protein complex (GO:0042611). Compared with vehicle controls, the cells treated with the combination of 5-FU and depsipeptide showed marked induction (3- to 8.5-fold) of expression of MHC class II genes, but not of MHC class I genes. Furthermore, our global analysis of gene expression, which was focused on genes involved in the molecular regulation of MHC class II genes, showed enhancement of pro-apoptotic PCAF and CIITA after the combination of 5-FU and depsipeptide. These results may indicate a closer relationship between elevation of MHC class II expression and cellular apoptosis induced by the combination of depsipeptide and 5-FU. To the best of our knowledge, this is the first study to report that the combination of 5-FU and depsipeptide induces human colon cancer cell apoptosis in a concerted manner with the induction of MHC

  2. Cryptographic Attacks and Countermeasures - A Mathematical View

    OpenAIRE

    Canright, David; Stanica, Pantelimon

    2009-01-01

    2009 CyberSecurity Summit, Naval Postgraduate School 1st NPS Cyber Summit was held at the Naval Postgraduate School in Monterey, California on October 29, 2009. Sessions were held on the following topics: security requirements, Kerchkoffs' principle, mathematics of cybersecurity, the data encryption standard, nonlinear equations, Cyber attacks on Bluetooth EQ, Crypto properties of S-boxes.

  3. Why Does Asthma Attack Severely at Night?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ The rhythmic changes of human physiological activities by day and at night may cause regular change of the patient's condition within one day. The following is the explanation with the theory of Chinese medicine for the reason why asthma attacks severely at night.

  4. Association between Terror Attacks and Suicide Attempts

    Science.gov (United States)

    Weizman, Tal; Yagil, Yaron; Schreiber, Shaul

    2009-01-01

    Based on Durkheim's "Control theory," we explored the association between frequency of terror attacks in Israel and the frequency of suicide attempts admitted to the Emergency Room of a major general hospital in Tel-Aviv (1999-2004). Analysis of the six-year study period as a whole revealed no significant correlation between the variables, with…

  5. Rhode Island School Terrorist Attack Preparedness

    Science.gov (United States)

    Dube, Michael W. M.

    2012-01-01

    This study examined the state of safety and terrorist attack preparedness in Rhode Island Schools as determined by Rhode Island school leader perceptions. The study is descriptive in nature as it gathers data to describe a particular event or situation. Using a researcher generated survey based on terrorist preparedness guidelines and suggestions…

  6. Chemical Attack of Malaysian Pozzolans Concrete

    Directory of Open Access Journals (Sweden)

    Mohd Hilton Ahmad

    2011-09-01

    Full Text Available Malaysia produces more than 10 million tonne of by-product from industrial sector per year. As the environmental impact concerns, more than half of the by-product can be recycled to be used as construction materials. One of them is pozzolan, a cement replacing material that can be used to enhance the properties of the concrete. This paper studies the chemical attack to local prozzolans concrete. The parameters studied include weight loss, length change, and residual strength of local pozzolans concrete after been exposed to severe environment. The specimen were tested under normal room temperature, exposed to magnesium sulfate, MgSO4. 2H2O where both sulfate attack and acid attack take place. Two series of pozzolans< which is Pulverized fly ash (PFA and Palm oil fuel ash (POFA were identified. Another series of admixture, Quarry Dust (QD from quarry waste that contain high amount of silica content also been carried out. Each series will study the effect of cement replacement percentage of 5%, 10% and 15%. The parameters were compared to conventional ordinary Portland cement (OPC concrete as control mix. Accelerated testing was conducted at 3, 7, 28, 56 and 90 days. The result shows that the local pozzolans concrete were found to be in good resistance against sulfate attack compared to conventional concrete. Compared to all series conducted, series of PFA replacement gave the best resistance followed by POFA and QD replacement series.

  7. Intrusion-Tolerant Replication under Attack

    Science.gov (United States)

    Kirsch, Jonathan

    2010-01-01

    Much of our critical infrastructure is controlled by large software systems whose participants are distributed across the Internet. As our dependence on these critical systems continues to grow, it becomes increasingly important that they meet strict availability and performance requirements, even in the face of malicious attacks, including those…

  8. Adversarial Feature Selection Against Evasion Attacks.

    Science.gov (United States)

    Zhang, Fei; Chan, Patrick P K; Biggio, Battista; Yeung, Daniel S; Roli, Fabio

    2016-03-01

    Pattern recognition and machine learning techniques have been increasingly adopted in adversarial settings such as spam, intrusion, and malware detection, although their security against well-crafted attacks that aim to evade detection by manipulating data at test time has not yet been thoroughly assessed. While previous work has been mainly focused on devising adversary-aware classification algorithms to counter evasion attempts, only few authors have considered the impact of using reduced feature sets on classifier security against the same attacks. An interesting, preliminary result is that classifier security to evasion may be even worsened by the application of feature selection. In this paper, we provide a more detailed investigation of this aspect, shedding some light on the security properties of feature selection against evasion attacks. Inspired by previous work on adversary-aware classifiers, we propose a novel adversary-aware feature selection model that can improve classifier security against evasion attacks, by incorporating specific assumptions on the adversary's data manipulation strategy. We focus on an efficient, wrapper-based implementation of our approach, and experimentally validate its soundness on different application examples, including spam and malware detection. PMID:25910268

  9. Shark Attack! Sinking Your Teeth into Anatomy.

    Science.gov (United States)

    House, Herbert

    2002-01-01

    Presents a real life shark attack story and studies arm reattachment surgery to teach human anatomy. Discusses how knowledge of anatomy can be put to use in the real world and how the arm functions. Includes teaching notes and suggestions for classroom management. (YDS)

  10. The diagnosis of transient ischemic attacks

    NARCIS (Netherlands)

    P.J. Koudstaal (Peter Jan)

    1989-01-01

    textabstractThe diagnosis of transient ischemic attack (TIA) is fraught with difficulty, since the diagnosis rests entirely upon the history of the patient's symptoms and the neurologist's skill in questioning the patient. The aim of this thesis is to investigate various measures to improve the reli

  11. Persistent cognitive impairment after transient ischemic attack

    NARCIS (Netherlands)

    Rooij, F.G. van; Schaapsmeerders, P.; Maaijwee, N.A.; Duijnhoven, D.A. van; Leeuw, F.E. de; Kessels, R.P.; Dijk, E.J. van

    2014-01-01

    BACKGROUND AND PURPOSE: By definition, the symptoms of a transient ischemic attack (TIA) subside completely within 24 hours. Imaging studies show signs of persistent ischemic tissue damage in a substantial amount of patients with TIA. Cerebral infarction can cause permanent cognitive impairment. Whe

  12. Persistent Cognitive Impairment After Transient Ischemic Attack

    NARCIS (Netherlands)

    Rooij, F.G. van; Schaapsmeerders, P.; Maaijwee, N.A.M.M.; Duijnhoven, D.A. van; de Leeuw, F.E.; Kessels, R.P.C.; Dijk, E.J. van

    2014-01-01

    Background and Purpose—By definition, the symptoms of a transient ischemic attack (TIA) subside completely within 24 hours. Imaging studies show signs of persistent ischemic tissue damage in a substantial amount of patients with TIA. Cerebral infarction can cause permanent cognitive impairment. Whet

  13. Activity Modelling and Comparative Evaluation of WSN MAC Security Attacks

    DEFF Research Database (Denmark)

    Pawar, Pranav M.; Nielsen, Rasmus Hjorth; Prasad, Neeli R.;

    2012-01-01

    and initiate security attacks that disturb the normal functioning of the network in a severe manner. Such attacks affect the performance of the network by increasing the energy consumption, by reducing throughput and by inducing long delays. Of all existing WSN attacks, MAC layer attacks are considered...... the most harmful as they directly affect the available resources and thus the nodes’ energy consumption. The first endeavour of this paper is to model the activities of MAC layer security attacks to understand the flow of activities taking place when mounting the attack and when actually executing it....... The second aim of the paper is to simulate these attacks on hybrid MAC mechanisms, which shows the performance degradation of aWSN under the considered attacks. The modelling and implementation of the security attacks give an actual view of the network which can be useful in further investigating secure...

  14. A graph based system for multi-stage attacks recognition

    Institute of Scientific and Technical Information of China (English)

    Safaa O. Al-Mamory; Zhai Jianhong; Zhang Hongli

    2008-01-01

    Building attack scenario is one of the most important aspects in network security. This paper proposed a system which collects intrusion alerts, clusters them as sub-attacks using alerts abstraction, aggregates the similar sub-attacks, and then correlates and generates correlation graphs. The scenarios were represented by alert classes instead of alerts themselves so as to reduce the required rules and have the ability of detecting new variations of attacks. The proposed system is capable of passing some of the missed attacks. To evaluate system effectiveness, it was tested with different datasets which contain multi-step attacks. Compressed and easily understandable correlation graphs which reflect attack scenarios were generated. The proposed system can correlate related alerts, uncover the attack strategies, and detect new variations of attacks.

  15. Antithrombotic Management of Patients with Nonvalvular Atrial Fibrillation and Ischemic Stroke or Transient Ischemic Attack: Executive Summary of the Korean Clinical Practice Guidelines for Stroke.

    Science.gov (United States)

    Jung, Keun-Hwa; Yu, Kyung-Ho; Kim, Young Dae; Park, Jong-Moo; Hong, Keun-Sik; Rha, Joung-Ho; Kwon, Sun U; Bae, Hee-Joon; Heo, Ji Hoe; Lee, Byung-Chul; Yoon, Byung-Woo

    2015-05-01

    Cardioembolic stroke related to nonvalvular atrial fibrillation is associated with a high recurrence rate and high mortality and morbidity. In this population, therefore, optimal anticoagulant therapy is required to prevent the occurrence of second stroke. Oral anticoagulant, warfarin has been traditionally used, but it is greatly limited by its narrow efficacy window, complex pharmacokinetics, and multiple drug interactions, thus requiring frequent blood monitoring. Recently, oral anticoagulants targeted for a specific coagulation component have been newly developed and tested in large clinical trials. Dabigatran, direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, inhibitors of factor Xa harbor great merits of rapid action time, short half-life, stable plasma concentration, and little drug interaction. Recently, large randomized clinical trials and meta-analyses have been published to show the efficacy and safety of the new oral anticoagulants compared with warfarin. Based on the results from recent clinical trials, we revised recommendations to apply optimal anticoagulant therapy in patients with nonvalvular atrial fibrillation and ischemic stroke or transient ischemic attack. PMID:26060808

  16. Polymorphic Attacks and Network Topology: Application of Concepts from Natural Systems

    Science.gov (United States)

    Rangan, Prahalad

    2010-01-01

    The growing complexity of interactions between computers and networks makes the subject of network security a very interesting one. As our dependence on the services provided by computing networks grows, so does our investment in such technology. In this situation, there is a greater risk of occurrence of targeted malicious attacks on computers…

  17. Role of CD59 in T cell activation induced by non-lethal complement attack

    Institute of Scientific and Technical Information of China (English)

    HAN Gen-cheng; BAI Yun; JIANG Man; LI Wan-ling; ZHU Xi-hua

    2001-01-01

    To study the mechanism ofT-cell activation induced by non-lethal complement attack and the role of CD59 in this process. Methods: Human CD59 and its transmembrane counterpart CD59TM cDNA were transfected into murine thymoma EL-4 cells. Activation and proliferation of EL-4 transfectants were observed with MTT assay.Results: Both CD59 and CD59 TM cDNA expressed on EL-4 cells effectively inhibited complement-mediated membrane damage. Cross-linking of CD59 with antibody induced activation of CD59/EL-4 cells but not CD59TM/EL-4cells. This effect was inhibited by Herbimycin A, a special protein tyrosine kinase (PTK) inhibitor. Non-lethal complement attack induced CD59/EL-4 but not CD59TM/EL-4 cell to proliferate, and this reaction was not blocked by Herbimycin A. Conclusion: CD59 takes part in T cell activation induced by non-lethal complement attack. The mechanisms of T cell activation induced by non-lethal complement attack are different from those by cross-linking of CD59.

  18. Recovery of human remains after shark attack.

    Science.gov (United States)

    Byard, Roger W; James, Ross A; Heath, Karen J

    2006-09-01

    Two cases of fatal shark attack are reported where the only tissues recovered were fragments of lung. Case 1: An 18-year-old male who was in the sea behind a boat was observed by friends to be taken by a great white shark (Carcharodon carcharias). The shark dragged him under the water and then, with a second shark, dismembered the body. Witnesses noted a large amount of blood and unrecognizable body parts coming to the surface. The only tissues recovered despite an intensive beach and sea search were 2 fragments of lung. Case 2: A 19-year-old male was attacked by a great white shark while diving. A witness saw the shark swim away with the victim's body in its mouth. Again, despite intensive beach and sea searches, the only tissue recovered was a single piece of lung, along with pieces of wetsuit and diving equipment. These cases indicate that the only tissue to escape being consumed or lost in fatal shark attacks, where there is a significant attack with dismemberment and disruption of the integrity of the body, may be lung. The buoyancy of aerated pulmonary tissue ensures that it rises quickly to the surface, where it may be recovered by searchers soon after the attack. Aeration of the lung would be in keeping with death from trauma rather than from drowning and may be a useful marker in unwitnessed deaths to separate ante- from postmortem injury, using only relatively small amounts of tissues. Early organ recovery enhances the identification of human tissues as the extent of morphologic alterations by putrefactive processes and sea scavengers will have been minimized. DNA testing is also possible on such recovered fragments, enabling confirmation of the identity of the victim. PMID:16936505

  19. Recovery of human remains after shark attack.

    Science.gov (United States)

    Byard, Roger W; James, Ross A; Heath, Karen J

    2006-09-01

    Two cases of fatal shark attack are reported where the only tissues recovered were fragments of lung. Case 1: An 18-year-old male who was in the sea behind a boat was observed by friends to be taken by a great white shark (Carcharodon carcharias). The shark dragged him under the water and then, with a second shark, dismembered the body. Witnesses noted a large amount of blood and unrecognizable body parts coming to the surface. The only tissues recovered despite an intensive beach and sea search were 2 fragments of lung. Case 2: A 19-year-old male was attacked by a great white shark while diving. A witness saw the shark swim away with the victim's body in its mouth. Again, despite intensive beach and sea searches, the only tissue recovered was a single piece of lung, along with pieces of wetsuit and diving equipment. These cases indicate that the only tissue to escape being consumed or lost in fatal shark attacks, where there is a significant attack with dismemberment and disruption of the integrity of the body, may be lung. The buoyancy of aerated pulmonary tissue ensures that it rises quickly to the surface, where it may be recovered by searchers soon after the attack. Aeration of the lung would be in keeping with death from trauma rather than from drowning and may be a useful marker in unwitnessed deaths to separate ante- from postmortem injury, using only relatively small amounts of tissues. Early organ recovery enhances the identification of human tissues as the extent of morphologic alterations by putrefactive processes and sea scavengers will have been minimized. DNA testing is also possible on such recovered fragments, enabling confirmation of the identity of the victim.

  20. Durability of Steel Fibres Reinforcement Concrete Beams in Chloride Environment Combined with Inhibitor

    Directory of Open Access Journals (Sweden)

    AbdelMonem Masmoudi

    2016-01-01

    Full Text Available This paper presented the effect of the combination of an inhibitor and steel fibre reinforced concrete (SFRC for concrete structures in chloride environments. Twelve beams were cast and tested to study their flexural behavior. The morphology of steel surfaces using the inhibitor after observing the scanning electron microscope showed a low layer of corrosion products. The steel surface immersed in the inhibitor free solution was seen to have been subject to chloride ions attacks as shown in this study. The interest to the field of the present study is the relatively higher durability of the performance when using the inhibitor. Crack width and crack spacing for beams under the same load showed that the use of SFRC with the inhibitor for concrete structures in chloride environments must have transferred tension across cracks that led to reducing crack spacing without any chloride ions attack.