Fuzzy MCDA for remediation of a uranium tailing

The Pridneprovsky Chemical Plant was a largest uranium processing enterprises, producing a huge amount of uranium residues. The Zapadnoe tailings site contains the majority of these residues. We propose a theoretical framework based on Multi-Criteria Decision Analysis and fuzzy logic to analyse different remediation alternatives for the Zapadnoe tailings, in which potentially conflicting economic, radiological, social and environmental objectives are simultaneously taken into account. An objective hierarchy is built that includes all the relevant aspects. Fuzzy rather than precise values are proposed for use to evaluate remediation alternatives against the different criteria and to quantify preferences, such as the weights representing the relative importance of criteria identified in the objective hierarchy. Finally, it is proposed that remediation alternatives should be evaluated by means of a fuzzy additive multi-attribute utility function and ranked on the basis of the respective trapezoidal fuzzy number representing their overall utility.

UAS See-and-Avoid Strategy using a Fuzzy Logic Controller Optimized by Cross-Entropy in Scaling Factors and Membership Functions.

This work aims to develop a novel Cross-Entropy (CE) optimization-based fuzzy controller for Unmanned Aerial Monocular Vision-IMU System (UAMVIS) to solve the seeand-avoid problem using its accurate autonomous localization information. The function of this fuzzy controller is regulating the heading of this system to avoid the obstacle, e.g. wall. In the Matlab Simulink-based training stages, the Scaling Factor (SF) is adjusted according to the specified task firstly, and then the Membership Function (MF) is tuned based on the optimized Scaling Factor to further improve the collison avoidance performance. After obtained the optimal SF and MF, 64% of rules has been reduced (from 125 rules to 45 rules), and a large number of real flight tests with a quadcopter have been done. The experimental results show that this approach precisely navigates the system to avoid the obstacle. To our best knowledge, this is the first work to present the optimized fuzzy controller for UAMVIS using Cross-Entropy method in Scaling Factors and Membership Functions optimization.

Defending against cybercrime: advances in the detection of malicious servers and the analysis of client-side vulnerabilities

Esta tesis se centra en el análisis de dos aspectos complementarios de la ciberdelincuencia (es decir, el crimen perpetrado a través de la red para ganar dinero). Estos dos aspectos son las máquinas infectadas utilizadas para obtener beneficios económicos de la delincuencia a través de diferentes acciones (como por ejemplo, clickfraud, DDoS, correo no deseado) y la infraestructura de servidores utilizados para gestionar estas máquinas (por ejemplo, C & C, servidores explotadores, servidores de monetización, redirectores). En la primera parte se investiga la exposición a las amenazas de los ordenadores victimas. Para realizar este análisis hemos utilizado los metadatos contenidos en WINE-BR conjunto de datos de Symantec. Este conjunto de datos contiene metadatos de instalación de ficheros ejecutables (por ejemplo, hash del fichero, su editor, fecha de instalación, nombre del fichero, la versión del fichero) proveniente de 8,4 millones de usuarios de Windows. Hemos asociado estos metadatos con las vulnerabilidades en el National Vulnerability Database (NVD) y en el Opens Sourced Vulnerability Database (OSVDB) con el fin de realizar un seguimiento de la decadencia de la vulnerabilidad en el tiempo y observar la rapidez de los usuarios a remiendar sus sistemas y, por tanto, su exposición a posibles ataques. Hemos identificado 3 factores que pueden influir en la actividad de parches de ordenadores victimas: código compartido, el tipo de usuario, exploits. Presentamos 2 nuevos ataques contra el código compartido y un análisis de cómo el conocimiento usuarios y la disponibilidad de exploit influyen en la actividad de aplicación de parches. Para las 80 vulnerabilidades en nuestra base de datos que afectan código compartido entre dos aplicaciones, el tiempo entre el parche libera en las diferentes aplicaciones es hasta 118 das (con una mediana de 11 das) En la segunda parte se proponen nuevas técnicas de sondeo activos para detectar y analizar las infraestructuras de servidores maliciosos. Aprovechamos técnicas de sondaje activo, para detectar servidores maliciosos en el internet. Empezamos con el análisis y la detección de operaciones de servidores explotadores. Como una operación identificamos los servidores que son controlados por las mismas personas y, posiblemente, participan en la misma campaña de infección. Hemos analizado un total de 500 servidores explotadores durante un período de 1 año, donde 2/3 de las operaciones tenían un único servidor y 1/2 por varios servidores. Hemos desarrollado la técnica para detectar servidores explotadores a diferentes tipologías de servidores, (por ejemplo, C & C, servidores de monetización, redirectores) y hemos logrado escala de Internet de sondeo para las distintas categorías de servidores maliciosos. Estas nuevas técnicas se han incorporado en una nueva herramienta llamada CyberProbe. Para detectar estos servidores hemos desarrollado una novedosa técnica llamada Adversarial Fingerprint Generation, que es una metodología para generar un modelo único de solicitud-respuesta para identificar la familia de servidores (es decir, el tipo y la operación que el servidor apartenece). A partir de una fichero de malware y un servidor activo de una determinada familia, CyberProbe puede generar un fingerprint válido para detectar todos los servidores vivos de esa familia. Hemos realizado 11 exploraciones en todo el Internet detectando 151 servidores maliciosos, de estos 151 servidores 75% son desconocidos a bases de datos publicas de servidores maliciosos. Otra cuestión que se plantea mientras se hace la detección de servidores maliciosos es que algunos de estos servidores podrán estar ocultos detrás de un proxy inverso silente. Para identificar la prevalencia de esta configuración de red y mejorar el capacidades de CyberProbe hemos desarrollado RevProbe una nueva herramienta a través del aprovechamiento de leakages en la configuración de la Web proxies inversa puede detectar proxies inversos. RevProbe identifica que el 16% de direcciones IP maliciosas activas analizadas corresponden a proxies inversos, que el 92% de ellos son silenciosos en comparación con 55% para los proxies inversos benignos, y que son utilizado principalmente para equilibrio de carga a través de múltiples servidores. ABSTRACT In this dissertation we investigate two fundamental aspects of cybercrime: the infection of machines used to monetize the crime and the malicious server infrastructures that are used to manage the infected machines. In the first part of this dissertation, we analyze how fast software vendors apply patches to secure client applications, identifying shared code as an important factor in patch deployment. Shared code is code present in multiple programs. When a vulnerability affects shared code the usual linear vulnerability life cycle is not anymore effective to describe how the patch deployment takes place. In this work we show which are the consequences of shared code vulnerabilities and we demonstrate two novel attacks that can be used to exploit this condition. In the second part of this dissertation we analyze malicious server infrastructures, our contributions are: a technique to cluster exploit server operations, a tool named CyberProbe to perform large scale detection of different malicious servers categories, and RevProbe a tool that detects silent reverse proxies. We start by identifying exploit server operations, that are, exploit servers managed by the same people. We investigate a total of 500 exploit servers over a period of more 13 months. We have collected malware from these servers and all the metadata related to the communication with the servers. Thanks to this metadata we have extracted different features to group together servers managed by the same entity (i.e., exploit server operation), we have discovered that 2/3 of the operations have a single server while 1/3 have multiple servers. Next, we present CyberProbe a tool that detects different malicious server types through a novel technique called adversarial fingerprint generation (AFG). The idea behind CyberProbe’s AFG is to run some piece of malware and observe its network communication towards malicious servers. Then it replays this communication to the malicious server and outputs a fingerprint (i.e. a port selection function, a probe generation function and a signature generation function). Once the fingerprint is generated CyberProbe scans the Internet with the fingerprint and finds all the servers of a given family. We have performed a total of 11 Internet wide scans finding 151 new servers starting with 15 seed servers. This gives to CyberProbe a 10 times amplification factor. Moreover we have compared CyberProbe with existing blacklists on the internet finding that only 40% of the server detected by CyberProbe were listed. To enhance the capabilities of CyberProbe we have developed RevProbe, a reverse proxy detection tool that can be integrated with CyberProbe to allow precise detection of silent reverse proxies used to hide malicious servers. RevProbe leverages leakage based detection techniques to detect if a malicious server is hidden behind a silent reverse proxy and the infrastructure of servers behind it. At the core of RevProbe is the analysis of differences in the traffic by interacting with a remote server.

Piezoelectric sensing and non-parametric statistical signal processing for health monitoring of hysteretic dampers used in seismic-resistant structures

The paper proposes a new application of non-parametric statistical processing of signals recorded from vibration tests for damage detection and evaluation on I-section steel segments. The steel segments investigated constitute the energy dissipating part of a new type of hysteretic damper that is used for passive control of buildings and civil engineering structures subjected to earthquake-type dynamic loadings. Two I-section steel segments with different levels of damage were instrumented with piezoceramic sensors and subjected to controlled white noise random vibrations. The signals recorded during the tests were processed using two non-parametric methods (the power spectral density method and the frequency response function method) that had never previously been applied to hysteretic dampers. The appropriateness of these methods for quantifying the level of damage on the I-shape steel segments is validated experimentally. Based on the results of the random vibrations, the paper proposes a new index that predicts the level of damage and the proximity of failure of the hysteretic damper

Control of pre-mRNA accumulation by the essential yeast protein Nrd1 requires high-affinity transcript binding and a domain implicated in RNA polymerase II association

Nrd1 is an essential yeast protein of unknown function that has an RNA recognition motif (RRM) in its carboxyl half and a putative RNA polymerase II-binding domain, the CTD-binding motif, at its amino terminus. Nrd1 mediates a severe reduction in pre-mRNA production from a reporter gene bearing an exogenous sequence element in its intron. The effect of the inserted element is highly sequence-specific and is accompanied by the appearance of 3′-truncated transcripts. We have proposed that Nrd1 binds to the exogenous sequence element in the nascent pre-mRNA during transcription, aided by the CTD-binding motif, and directs 3′-end formation a short distance downstream. Here we show that highly purified Nrd1 carboxyl half binds tightly to the RNA element in vitro with sequence specificity that correlates with the efficiency of cis-element-directed down-regulation in vivo. A large deletion in the CTD-binding motif blocks down-regulation but does not affect the essential function of Nrd1. Furthermore, a nonsense mutant allele that produces truncated Nrd1 protein lacking the RRM has a dominant-negative effect on down-regulation but not on cell growth. Viability of this and several other nonsense alleles of Nrd1 appears to require translational readthrough, which in one case is extremely efficient. Thus the CTD-binding motif of Nrd1 is important for pre-mRNA down-regulation but is not required for the essential function of Nrd1. In contrast, the RNA-binding activity of Nrd1 appears to be required both for down-regulation and for its essential function.

Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype

Searching for nervous system candidates that could directly induce T cell cytokine secretion, I tested four neuropeptides (NPs): somatostatin, calcitonin gene-related peptide, neuropeptide Y, and substance P. Comparing neuropeptide-driven versus classical antigen-driven cytokine secretion from T helper cells Th0, Th1, and Th2 autoimmune-related T cell populations, I show that the tested NPs, in the absence of any additional factors, directly induce a marked secretion of cytokines [interleukin 2 (IL-2), interferon-γ, IL-4, and IL-10) from T cells. Furthermore, NPs drive distinct Th1 and Th2 populations to a “forbidden” cytokine secretion: secretion of Th2 cytokines from a Th1 T cell line and vice versa. Such a phenomenon cannot be induced by classical antigenic stimulation. My study suggests that the nervous system, through NPs interacting with their specific T cell-expressed receptors, can lead to the secretion of both typical and atypical cytokines, to the breakdown of the commitment to a distinct Th phenotype, and a potentially altered function and destiny of T cells in vivo.

Glycine-induced long-term potentiation is associated with structural and functional modifications of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors

Global long-term potentiation (LTP) was induced in organotypic hippocampal slice cultures by a brief application of 10 mM glycine. Glycine-induced LTP was occluded by previous theta burst stimulation-induced potentiation, indicating that both phenomena share similar cellular processes. Glycine-induced LTP was associated with increased [3H]α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) binding in membrane fractions as well as increased amount of a selective spectrin breakdown product generated by calpain-mediated spectrin proteolysis. Antibodies against the C-terminal (C-Ab) and N-terminal (N-Ab) domains of GluR1 subunits were used to evaluate structural changes in AMPA receptor properties resulting from glycine-induced LTP. No quantitative or qualitative changes were observed in Western blots from membrane fractions prepared from glycine-treated slices with C-Ab. In contrast, Western blots stained with N-Ab revealed the formation of a 98-kDa species of GluR1 subunits as well as an increased amount of immunoreactivity after glycine-induced LTP. The amount of spectrin breakdown product was positively correlated with the amount of the 98-kDa species of GluR1 after glycine treatment. Functional modifications of AMPA receptors were evaluated by determining changes in the effect of pressure-applied AMPA on synaptic responses before and after glycine-induced LTP. Glycine treatment produced a significant increase in AMPA receptor function after potentiation that correlated with the degree of potentiation. The results indicate that LTP induction produces calpain activation, truncation of the C-Ab domain of GluR1 subunits of AMPA receptors, and increased AMPA receptor function. They also suggest that insertion of new receptors takes place after LTP induction.

ApoNifH functions in iron–molybdenum cofactor synthesis and apodinitrogenase maturation

NifH (dinitrogenase reductase) has three important roles in the nitrogenase enzyme system. In addition to its role as the obligate electron donor to dinitrogenase, NifH is required for the iron–molybdenum cofactor (FeMo-co) synthesis and apodinitrogenase maturation. We have investigated the requirement of the Fe–S cluster of NifH for these processes by preparing apoNifH. The 4Fe–4S cluster of NifH was removed by chelation of the cluster with α, α′-bipyridyl. The resulting apoNifH was tested in in vitro FeMo-co synthesis and apodinitrogenase maturation reactions and was found to function in both these processes. Thus, the presence of a redox active 4Fe–4S cluster in NifH is not required for its function in FeMo-co synthesis and in apodinitrogenase maturation. This, in turn, implies that the role of NifH in these processes is not one of electron transfer or of iron or sulfur donation.

Increase of intracellular Ca2+ and relocation of E-cadherin during experimental decompaction of mouse embryos

To determine the role of intracellular Ca2+ in compaction, the first morphogenetic event in embryogenesis, we analyzed preimplantation mouse embryos under several decompacting conditions, including depletion of extracellular Ca2+, blocking of Ca2+ channels, and inhibition of microfilaments, calmodulin, and intracellular Ca2+ release. Those treatments induced decompaction of mouse morulae and simultaneously induced changes in cytosolic free Ca2+ concentration and deregionalization of E-cadherin and fodrin. When morulae were allowed to recompact, the location of both proteins recovered. In contrast, actin did not change its cortical location with compaction nor with decompaction-recompaction. Calmodulin localized in areas opposite to cell–cell contacts in eight-cell stage embryos before and after compaction. Inhibition of calmodulin with trifluoperazine induced its delocalization while morulae decompacted. A nonspecific rise of intracellular free Ca2+ provoked by ionomycin did not affect the compacted shape. Moreover, the same decompacting treatments when applied to uncompacted embryos did not produce any change in intracellular Ca2+. Our results demonstrate that in preimplantation mouse embryos experimentally induced stage-specific changes of cell shape are accompanied by changes of intracellular free Ca2+ and redistribution of the cytoskeleton-related proteins E-cadherin, fodrin, and calmodulin. We conclude that intracellular Ca2+ specifically is involved in compaction and probably regulates the function and localization of cytoskeleton elements.

Distinct roles for E2F proteins in cell growth control and apoptosis

E2F transcription activity is composed of a family of heterodimers encoded by distinct genes. Through the overproduction of each of the five known E2F proteins in mammalian cells, we demonstrate that a large number of genes encoding proteins important for cell cycle regulation and DNA replication can be activated by the E2F proteins and that there are distinct specificities in the activation of these genes by individual E2F family members. Coexpression of each E2F protein with the DP1 heterodimeric partner does not significantly alter this specificity. We also find that only E2F1 overexpression induces cells to undergo apoptosis, despite the fact that at least two other E2F family members, E2F2 and E2F3, are equally capable of inducing S phase. The ability of E2F1 to induce apoptosis appears to result from the specific induction of an apoptosis-promoting activity rather than the lack of induction of a survival activity, because co-expression of E2F2 and E2F3 does not rescue cells from E2F1-mediated apoptosis. We conclude that E2F family members play distinct roles in cell cycle control and that E2F1 may function as a specific signal for the initiation of an apoptosis pathway that must normally be blocked for a productive proliferation event.

Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion

A cell’s ability to effectively communicate with a neighboring cell is essential for tissue function and ultimately for the organism to which it belongs. One important mode of intercellular communication is the release of soluble cyto- and chemokines. Once secreted, these signaling molecules diffuse through the surrounding medium and eventually bind to neighboring cell’s receptors whereby the signal is received. This mode of communication is governed both by physicochemical transport processes and cellular secretion rates, which in turn are determined by genetic and biochemical processes. The characteristics of transport processes have been known for some time, and information on the genetic and biochemical determinants of cellular function is rapidly growing. Simultaneous quantitative analysis of the two is required to systematically evaluate the nature and limitations of intercellular signaling. The present study uses a solitary cell model to estimate effective communication distances over which a single cell can meaningfully propagate a soluble signal. The analysis reveals that: (i) this process is governed by a single, key, dimensionless group that is a ratio of biological parameters and physicochemical determinants; (ii) this ratio has a maximal value; (iii) for realistic values of the parameters contained in this dimensionless group, it is estimated that the domain that a single cell can effectively communicate in is ≈250 μm in size; and (iv) the communication within this domain takes place in 10–30 minutes. These results have fundamental implications for interpretation of organ physiology and for engineering tissue function ex vivo.

RhoA-Dependent Phosphorylation and Relocalization of ERM Proteins into Apical Membrane/Actin Protrusions in Fibroblasts

The ERM proteins (ezrin, radixin, and moesin) are a group of band 4.1-related proteins that are proposed to function as membrane/cytoskeletal linkers. Previous biochemical studies have implicated RhoA in regulating the association of ERM proteins with their membrane targets. However, the specific effect and mechanism of action of this regulation is unclear. We show that lysophosphatidic acid stimulation of serum-starved NIH3T3 cells resulted in relocalization of radixin into apical membrane/actin protrusions, which was blocked by inactivation of Rho by C3 transferase. An activated allele of RhoA, but not Rac or CDC42Hs, was sufficient to induce apical membrane/actin protrusions and localize radixin or moesin into these structures in both Rat1 and NIH3T3 cells. Lysophosphatidic acid treatment led to phosphorylation of radixin preceding its redistribution into apical protrusions. Significantly, cotransfection of RhoAV14 or C3 transferase with radixin and moesin revealed that RhoA activity is necessary and sufficient for their phosphorylation. These findings reveal a novel function of RhoA in reorganizing the apical actin cytoskeleton and suggest that this function may be mediated through phosphorylation of ERM proteins.

Ras Pathway Activates Epithelial Na+ Channel and Decreases Its Surface Expression in Xenopus Oocytes

The small G protein K-Ras2A is rapidly induced by aldosterone in A6 epithelia. In these Xenopus sodium reabsorbing cells, aldosterone rapidly activates preexisting epithelial Na+ channels (XENaC) via a transcriptionally mediated mechanism. In the Xenopus oocytes expression system, we tested whether the K-Ras2A pathway impacts on XENaC activity by expressing XENaC alone or together with XK-Ras2A rendered constitutively active (XK-Ras2AG12V). As a second control, XENaC-expressing oocytes were treated with progesterone, a sex steroid that induces maturation of the oocytes similarly to activated Ras. Progesterone or XK-Ras2AG12V led to oocyte maturation characterized by a decrease in surface area and endogenous Na+ pump function. In both conditions, the surface expression of exogenous XENaC′s was also decreased; however, in comparison with progesterone-treated oocytes, XK-ras2AG12V-coinjected oocytes expressed a fivefold higher XENaC-mediated macroscopic Na+ current that was as high as that of control oocytes. Thus, the Na+ current per surface-expressed XENaC was increased by XK-Ras2AG12V. The chemical driving force for Na+ influx was not changed, suggesting that XK-Ras2AG12V increased the mean activity of XENaCs at the oocyte surface. These observations raise the possibility that XK-Ras2A, which is the first regulatory protein known to be transcriptionally induced by aldosterone, could play a role in the control of XENaC function in aldosterone target cells.

Molecular basis for a link between complement and the vascular complications of diabetes

Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes.

Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin

Pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 (PBSF/SDF-1) is a member of the CXC group of chemokines that is initially identified as a bone marrow stromal cell-derived factor and as a pre-B-cell stimulatory factor. Although most chemokines are thought to be inducible inflammatory mediators, PBSF/SDF-1 is essential for perinatal viability, B lymphopoiesis, bone marrow myelopoiesis, and cardiac ventricular septal formation, and it has chemotactic activities on resting lymphocytes and monocytes. In this paper, we have isolated a cDNA that encodes a seven transmembrane-spanning-domain receptor, designated pre-B-cell-derived chemokine receptor (PB-CKR) from a murine pre-B-cell clone, DW34. The deduced amino acid sequence has 90% identity with that of a HUMSTSR/fusin, a human immunodeficiency virus 1 (HIV-1) entry coreceptor. However, the second extracellular region has lower identity (67%) compared with HUMSTSR/fusin. PB-CKR is expressed during embryo genesis and in many organs and T cells of adult mice. Murine PBSF/SDF-1 induced an increase in intracellular free Ca2+ in DW34 cells and PB-CKR-transfected Chinese hamster ovary (CHO) cells, suggesting that PB-CKR is a functional receptor for murine PBSF/SDF-1. Murine PBSF/SDF-1 also induced Ca2+ influx in fusin-transfected CHO cells. On the other hand, considering previous results that HIV-1 does not enter murine T cells that expressed human CD4, PB-CKR may not support HIV-1 infection. Thus, PB-CKR will be an important tool for functional mapping of HIV-1 entry coreceptor fusin and for understanding the function of PBSF/SDF-1 further.