An improved method for discovering link criticality in transport networks

Quantitatively assessing the importance or criticality of each link in a network is of practical value to operators, as that can help them to increase the network's resilience, provide more efficient services, or improve some other aspect of the service. Betweenness is a graph-theoretical measure of centrality that can be applied to communication networks to evaluate link importance. However, as we illustrate in this paper, the basic definition of betweenness centrality produces inaccurate estimations as it does not take into account some aspects relevant to networking, such as the heterogeneity in link capacity or the difference between node-pairs in their contribution to the total traffic. A new algorithm for discovering link centrality in transport networks is proposed in this paper. It requires only static or semi-static network and topology attributes, and yet produces estimations of good accuracy, as verified through extensive simulations. Its potential value is demonstrated by an example application. In the example, the simple shortest-path routing algorithm is improved in such a way that it outperforms other more advanced algorithms in terms of blocking ratio

Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells.

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigen-specific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4(+)CD25(-) T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO(+)CCR7(-) memory cells, and had a CD4(high), CD25(+), Foxp3(+), and CD62L (L-selectin)(+) phenotype. Although these CD4(high)CD25(+)Foxp3(+) alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases.

Comparison of topography- and aperture-dependent motion compensation algorithms for airborne SAR

This letter presents a comparison between threeFourier-based motion compensation (MoCo) algorithms forairborne synthetic aperture radar (SAR) systems. These algorithmscircumvent the limitations of conventional MoCo, namelythe assumption of a reference height and the beam-center approximation.All these approaches rely on the inherent time–frequencyrelation in SAR systems but exploit it differently, with the consequentdifferences in accuracy and computational burden. Aftera brief overview of the three approaches, the performance ofeach algorithm is analyzed with respect to azimuthal topographyaccommodation, angle accommodation, and maximum frequencyof track deviations with which the algorithm can cope. Also, ananalysis on the computational complexity is presented. Quantitativeresults are shown using real data acquired by the ExperimentalSAR system of the German Aerospace Center (DLR).

Efficient in vivo induction of CTL by cell-associated covalent H-2Kd-peptide complexes.

A novel procedure is presented describing the induction of antigen-specific cytolytic T lymphocytes (CTL) in vivo, that uses as immunogen syngeneic Concanavalin A stimulated spleen cells expressing H-2Kd (Kd) molecules photocrosslinked with a photoreactive peptide derivative. The Kd restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) was conjugated with photoreactive iodo-4-azidosalicylic acid (IASA) at the NH2-terminus and with 4-azidobenzoic acid (ABA) at the TCR contact residue Lys259 to make IASA-YIPSAEK(ABA)I. Selective photoactivation of the IASA group allowed specific photoaffinity labeling of cell-associated Kd molecules. Optimal peptide derivative binding to Kd molecules of concanavalin A stimulated spleen cells was obtained upon 4-6 h incubation at 26 degrees C in the presence of human beta 2 microglobulin. Photocrosslinking prevented the rapid dissociation of cell-associated Kd-peptide derivative complexes at 37 degrees C. The photoaffinity labeled cells were injected i.p. into syngeneic recipients. After 10 days, the peritoneal exudate lymphocytes were harvested and in vitro stimulated with peptide derivative pulsed P815 mastocytoma cells. The resulting bulk cultures displayed high cytolytic activity that was specific for IASA-YIPSAEK(ABA)I and YIPSAEK(ABA)I. In contrast, peritoneal exudate lymphocytes from mice inoculated with concanavalin A blasts that were pulsed, but not photocrosslinked, with IASA-YIPSAEK(ABA)I expressed only marginal levels of IASA-YIPSAEK(ABA)I-specific cytolytic activity. This immunization strategy, using neither adjuvants nor potentially hazardous transfected/transformed cells, is safe and should be universally applicable.

Using free data mining software and clustering algorithms to find predictors from student qualifications

In this project a research both in finding predictors via clustering techniques and in reviewing the Data Mining free software is achieved. The research is based in a case of study, from where additionally to the KDD free software used by the scientific community; a new free tool for pre-processing the data is presented. The predictors are intended for the e-learning domain as the data from where these predictors have to be inferred are student qualifications from different e-learning environments. Through our case of study not only clustering algorithms are tested but also additional goals are proposed.

CHD8 associates with human Staf and contributes to efficient U6 RNA polymerase III transcription.

Chromatin remodeling and histone modification are essential for eukaryotic transcription regulation, but little is known about chromatin-modifying activities acting on RNA polymerase III (Pol III)-transcribed genes. The human U6 small nuclear RNA promoter, located 5' of the transcription start site, consists of a core region directing basal transcription and an activating region that recruits the transcription factors Oct-1 and Staf (ZNF143). Oct-1 activates transcription in part by helping recruit core binding factors, but nothing is known about the mechanisms of transcription activation by Staf. We show that Staf activates U6 transcription from a preassembled chromatin template in vitro and associates with several proteins linked to chromatin modification, among them chromodomain-helicase-DNA binding protein 8 (CHD8). CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters. Thus, Pol III transcription from type 3 promoters uses some of the same factors used for chromatin remodeling at Pol II promoters.

CD8beta endows CD8 with efficient coreceptor function by coupling T cell receptor/CD3 to raft-associated CD8/p56(lck) complexes.

The extraordinary sensitivity of CD8+ T cells to recognize antigen impinges to a large extent on the coreceptor CD8. While several studies have shown that the CD8beta chain endows CD8 with efficient coreceptor function, the molecular basis for this is enigmatic. Here we report that cell-associated CD8alphabeta, but not CD8alphaalpha or soluble CD8alphabeta, substantially increases the avidity of T cell receptor (TCR)-ligand binding. To elucidate how the cytoplasmic and transmembrane portions of CD8beta endow CD8 with efficient coreceptor function, we examined T1.4 T cell hybridomas transfected with various CD8beta constructs. T1.4 hybridomas recognize a photoreactive Plasmodium berghei circumsporozoite (PbCS) peptide derivative (PbCS (4-azidobezoic acid [ABA])) in the context of H-2K(d), and permit assessment of TCR-ligand binding by TCR photoaffinity labeling. We find that the cytoplasmic portion of CD8beta, mainly due to its palmitoylation, mediates partitioning of CD8 in lipid rafts, where it efficiently associates with p56(lck). In addition, the cytoplasmic portion of CD8beta mediates constitutive association of CD8 with TCR/CD3. The resulting TCR-CD8 adducts exhibit high affinity for major histocompatibility complex (MHC)-peptide. Importantly, because CD8alphabeta partitions in rafts, its interaction with TCR/CD3 promotes raft association of TCR/CD3. Engagement of these TCR/CD3-CD8/lck adducts by multimeric MHC-peptide induces activation of p56(lck) in rafts, which in turn phosphorylates CD3 and initiates T cell activation.

Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus-associated genital tumors.

Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE71CD81 and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.

Discovery of catalases in members of the Chlamydiales order.

Catalase is an important virulence factor for survival in macrophages and other phagocytic cells. In Chlamydiaceae, no catalase had been described so far. With the sequencing and annotation of the full genomes of Chlamydia-related bacteria, the presence of different catalase-encoding genes has been documented. However, their distribution in the Chlamydiales order and the functionality of these catalases remain unknown. Phylogeny of chlamydial catalases was inferred using MrBayes, maximum likelihood, and maximum parsimony algorithms, allowing the description of three clade 3 and two clade 2 catalases. Only monofunctional catalases were found (no catalase-peroxidase or Mn-catalase). All presented a conserved catalytic domain and tertiary structure. Enzymatic activity of cloned chlamydial catalases was assessed by measuring hydrogen peroxide degradation. The catalases are enzymatically active with different efficiencies. The catalase of Parachlamydia acanthamoebae is the least efficient of all (its catalytic activity was 2 logs lower than that of Pseudomonas aeruginosa). Based on the phylogenetic analysis, we hypothesize that an ancestral class 2 catalase probably was present in the common ancestor of all current Chlamydiales but was retained only in Criblamydia sequanensis and Neochlamydia hartmannellae. The catalases of class 3, present in Estrella lausannensis and Parachlamydia acanthamoebae, probably were acquired by lateral gene transfer from Rhizobiales, whereas for Waddlia chondrophila they likely originated from Legionellales or Actinomycetales. The acquisition of catalases on several occasions in the Chlamydiales suggests the importance of this enzyme for the bacteria in their host environment.

Is there an efficient trap or collection method for sampling Anopheles darlingi and other malaria vectors that can describe the essential parameters affecting transmission dynamics as effectively as human landing catches? - A Review

Distribution, abundance, feeding behaviour, host preference, parity status and human-biting and infection rates are among the medical entomological parameters evaluated when determining the vector capacity of mosquito species. To evaluate these parameters, mosquitoes must be collected using an appropriate method. Malaria is primarily transmitted by anthropophilic and synanthropic anophelines. Thus, collection methods must result in the identification of the anthropophilic species and efficiently evaluate the parameters involved in malaria transmission dynamics. Consequently, human landing catches would be the most appropriate method if not for their inherent risk. The choice of alternative anopheline collection methods, such as traps, must consider their effectiveness in reproducing the efficiency of human attraction. Collection methods lure mosquitoes by using a mixture of olfactory, visual and thermal cues. Here, we reviewed, classified and compared the efficiency of anopheline collection methods, with an emphasis on Neotropical anthropophilic species, especially Anopheles darlingi, in distinct malaria epidemiological conditions in Brazil.

Clustering algorithms for anti-money laundering using graph theory and social network analysis

HEMOLIA (a project under European community’s 7th framework programme) is a new generation Anti-Money Laundering (AML) intelligent multi-agent alert and investigation system which in addition to the traditional financial data makes extensive use of modern society’s huge telecom data source, thereby opening up a new dimension of capabilities to all Money Laundering fighters (FIUs, LEAs) and Financial Institutes (Banks, Insurance Companies, etc.). This Master-Thesis project is done at AIA, one of the partners for the HEMOLIA project in Barcelona. The objective of this thesis is to find the clusters in a network drawn by using the financial data. An extensive literature survey has been carried out and several standard algorithms related to networks have been studied and implemented. The clustering problem is a NP-hard problem and several algorithms like K-Means and Hierarchical clustering are being implemented for studying several problems relating to sociology, evolution, anthropology etc. However, these algorithms have certain drawbacks which make them very difficult to implement. The thesis suggests (a) a possible improvement to the K-Means algorithm, (b) a novel approach to the clustering problem using the Genetic Algorithms and (c) a new algorithm for finding the cluster of a node using the Genetic Algorithm.

Multicast algorithms evaluation using an adaptative routing in ATM networks

This paper proposes a multicast implementation based on adaptive routing with anticipated calculation. Three different cost measures for a point-to-multipoint connection: bandwidth cost, connection establishment cost and switching cost can be considered. The application of the method based on pre-evaluated routing tables makes possible the reduction of bandwidth cost and connection establishment cost individually

New perspectives in the use of ink evidence in forensic science: Part II. Development and testing of mathematical algorithms for the automatic comparison of ink samples analysed by HPTLC

In the first part of this research, three stages were stated for a program to increase the information extracted from ink evidence and maximise its usefulness to the criminal and civil justice system. These stages are (a) develop a standard methodology for analysing ink samples by high-performance thin layer chromatography (HPTLC) in reproducible way, when ink samples are analysed at different time, locations and by different examiners; (b) compare automatically and objectively ink samples; and (c) define and evaluate theoretical framework for the use of ink evidence in forensic context. This report focuses on the second of the three stages. Using the calibration and acquisition process described in the previous report, mathematical algorithms are proposed to automatically and objectively compare ink samples. The performances of these algorithms are systematically studied for various chemical and forensic conditions using standard performance tests commonly used in biometrics studies. The results show that different algorithms are best suited for different tasks. Finally, this report demonstrates how modern analytical and computer technology can be used in the field of ink examination and how tools developed and successfully applied in other fields of forensic science can help maximising its impact within the field of questioned documents.

Insulated retroviral vectors towards safe and efficient genetic modification of stem cells

In otherwise successful gene therapy trials for the treatment of SCID patients and others, insertional mutagenesis has resulted in leukemia development. Besides the integration of vectors that including strong enhancers, more recently, SIN-vectors have been shown to partially retain oncogenic potential. The identification of genetic elements which would both prevent such activation effects and shield the transgene from silencing, is a main challenge. Previous attempts met with difficulties in producing the vectors and poor efficacy of the insulators (GIE). The improvement of integrating vectors safety has been investigated using new candidate synthetic GIEs. The latter have been introduced in retroviral and lentiviral vectors. Native LTRs, SIN-LTRs, and SIN-insulated constructs have been designed and compared, using two sets of internal promoter, i.e. strong and housekeeping. We could establish that a specific insulator translates at best into functional activity and boundary effect in both vector types. We could also determine that other genetic elements are key determinants in order to achieve accurate expression and viral titre, from these insulated vectors. A dramatic shift in the expression profile is observed in target cells, with a homogenous pattern including data on both cell-lines and primary HSCs from cord blood. The assessment of potential genotoxicity will be presented, based on the comparison of the integration patterns ingenuity in human target cells sampled over a three months period with both reference LTRs and SIN versus test insulated vectors, using high-throughput pyro-sequencing.