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Software Defined Networking (SDN) is a networking architecture within the control is centralized through a software-based controller. Hence, the controller represents a single point of attack which makes the controller a preferred target in case of attack. In previous work, an observer has been introduced in order to detect any anomalies in the network control (in particular, in the data planes which are set up). The detection method is based on the assumption that the observer captures all the packets sent and received by the controller. This paper introduces an extension of the detection approach to improve the robustness in case of partial or parsimonious observation, more specifically when the complete data plane cannot be observed. The evaluation of the consistency of the data plane is adapted by definition of necessary condition which permits to conclude that the data plane is inconsistent. In the absence of evidence, a function which permits to compute the level of confidence in the consistency of the data plane is introduced. The efficiency and the limitations of such method is discussed on a case study.

Software Defined Networking (SDN) is a networking architecture within the control is centralized through a software-based controller. Thus, being a single point of attack makes it the preferred target in case of attack. Multi controller architecture has been considered to reinforce the control plane. However, the communication interface between the controller is a security threat. We already propose a dual controller architecture, one nominal controller which is in charge of the data plane computation plus a second one which is in charge of the detection of anomalies in the decisions taken by the first controller. Previous work considered a deterministic control and this paper extends to the case of a non-determinist algorithm. In this objective we introduce a multi-criteria detection approach and we developed two approaches: verifying the consistency of the performance of the decisions taken and verifying the consistency of the sequence of decisions of the controller. We tested the proposition on a study case.

Software Defined Networking (SDN) is a networking architecture within the control is centralized through a software-based controller. Like Cyber-Physical Systems manager, this centralization eases the support of advanced application. Being a single point of attack makes the controller a preferred target in case of attack. To enhance the control plane against cyber-attacks, an observer is introduced and is in charge of the detection of cyber-attacks on the nominal controller. In this objective, a detection of anomalies method in the activity of the control is proposed. This activity is defined as the events at the interface of communication between the controller and the network plant. In this paper, a non-deterministic control is considered which means that the decisions are stochastic. Hence, a probabilistic approach is proposed which aims to evaluate the deviation of the likelihood of the sequence of decisions taken by the controller. The formalism used to determine the likelihood is the Hidden Markov Model which permits to infer over the internal states of the controller through the observations. This method is discussed on a network case study.

Software Defined Networking is a concept within the networking field which proposed a centralized control considering the control and data planes. To overcome the safety and security threats, solutions might be divided into two categories: enforcing the controller to make it more robust or the architecture using a multi-controller approach. This work aims to pave the way for a multi-controller architecture without East-West interface to avoid the spreading of an attack. There is one nominal controller in charge of the control while the second observes the traffic at the Southbound interface to detect anomalies of control. A detection method is introduced theoretically and relies on Intrusion Detection System theory, more precisely the specification-based. Here, the specification is a template determined through a projection function of the control logic. The template is compared to the activity of the command observed such that any deviation generates an alarm. The method is finally explained in use cases.

After highlighting the difficulties encountered while implementing a supervisor on actual industrial controllers and different approaches already suggested to tackle them, this paper presents a signal-interpreted approach to the Supervisory Control Theory (SCT) framework. This work focuses on further developments of this approach for reactive systems. Due to fundamental differences between event- and signal-based approaches, new algorithms have to be implemented to apply an SCT approach on the basis of signal-interpreted Boolean finite automata extended with variables. Also, compared to a previous version of this approach, partially controllable signals are introduced.

Background: Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation. Results: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue. Conclusions: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.

Loss of muscle mass and function is a severe complication in patients with stroke that contributes to promoting physical inactivity and disability. The deleterious consequences of skeletal muscle mass loss underline the necessity to identity the molecular mechanisms involved in skeletal muscle atrophy after cerebral ischemia.

Purpose:Newborn screening (NBS) for cystic fibrosis (CF) was implemented throughout France in 2002. It involves a four-tiered procedure: immunoreactive trypsin (IRT)/DNA/IRT/sweat test was implemented throughout France in 2002. The aim of this study was to assess the performance of molecular CFTR gene analysis from the French NBS cohort, to evaluate CF incidence, mutation detection rate, and allelic heterogeneity.Methods:During the 8-year period, 5,947,148 newborns were screened for cystic fibrosis. The data were collected by the Association Française pour le Dépistage et la Prévention des Handicaps de l’Enfant. The mutations identified were classified into four groups based on their potential for causing disease, and a diagnostic algorithm was proposed.Results:Combining the genetic and sweat test results, 1,160 neonates were diagnosed as having cystic fibrosis. The corresponding incidence, including both the meconium ileus (MI) and false-negative cases, was calculated at 1 in 4,726 live births. The CF30 kit, completed with a comprehensive CFTR gene analysis, provides an excellent detection rate of 99.77% for the mutated alleles, enabling the identification of a complete genotype in 99.55% of affected neonates. With more than 200 different mutations characterized, we confirmed the French allelic heterogeneity.Conclusion:The very good sensitivity, specificity, and positive predictive value obtained suggest that the four-tiered IRT/DNA/IRT/sweat test procedure may provide an effective strategy for newborn screening for cystic fibrosis.Genet Med 17 2, 108–116.

This paper describes the design of a system to monitor floor vibrations in an office building and an analysis of several months worth of collected data. Floors of modern office buildings are prone to occupant-induced vibrations. The contributing factors include long spans, slender and flexible designs, use of lightweight materials and low damping. As a result, resonant frequencies often fall in the range easily excited by normal footfall loading, creating potential serviceability problems due to undesirable levels of vibrations. This study investigates in-situ performance of a non-composite timber-concrete floor located in a recently constructed innovative multi-storey office building. The floor monitoring system consists of several displacement transducers to measure long-term deformations due to timber and concrete creep and three accelerometers to measure responses to walking forces, the latter being the focus of this paper. Floor response is typically complex and multimodal and the optimal accelerometer locations were decided with the help of the effective independence-driving point residue (EfI-DPR) technique. A novel approach to the EfI-DPR method proposed here uses a combinatorial search algorithm that increases the chances of obtaining the globally optimal solution. Several months worth of data collected by the monitoring system were analyzed using available industry guidelines, including ISO2631-1:1997(E), ISO10137:2007(E) and SCI Publication P354. This enabled the evaluation of the floor performance under real operating conditions.

An innovative three-story timber building, using self-centering, post-tensioned timber shear walls as the main horizontal load resisting system and lightweight non-composite timber-concrete floors, has recently been completed in Nelson, New Zealand. It is expected to be the trailblazer for similar but taller structures to be more widely adopted. Performance based standards require an advanced understanding of building responses and in order to meet the need for in-situ performance data the building has been subjected to forced vibration testing and instrumented for continuous monitoring using a total of approximately 90 data channels to capture its dynamic and long-term responses. The first part of the paper presents a brief discussion of the existing research on the seismic performance of timber frame buildings and footfall induced floor vibrations. An outline of the building structural system, focusing on the novel design solutions, is then discussed. This is followed by the description of the monitoring system. The analysis of monitoring results starts with a discussion of the monitoring of long-term deformations. Next, the assessment of the floor vibration serviceability performance is outlined. Then, the forced vibration tests conducted on the whole building at different construction stages are reviewed. The system identification results from seismic shaking records are also discussed. Finally, updating of a finite element model of the building is conducted.

A low cost and low temperature MEMS transfer process is presented. The process is based on adhesion control of molded electroplated Ni microstructures on donor wafer by using plasma deposited fluorocarbon film. Adhesive bonding of the microstructures on the target wafer using BCB sealing enables mechanical tearing out from the donor wafer. This proposed process has allowed us to realize from 7 um down to 700 nm thick Ni patterns on Si, Pyrex glass wafers and Kapton foils. Multiple transfers lead to Ni stacked microstructures. Because this process is simple and only involves a low temperature (250degC) heating of the host wafer, it is highly versatile and suitable for various applications and brings new perspectives towards 3D integration of MEMS/NEMS.

Abstract: A method for the calibration of closely spaced multiple hot-film sensor (MHFS) arrays of nickel-on-polyimide-substrate type was presented in this paper. The hot-film sensors were calibrated individually and in situ against the values of the wall-shear stresses determined from boundary-layer velocity profiles (developed on the front portion of a circular cylinder) through a specially designed wall-mounted hot-wire probe. The accuracy and feasibility of the present method was examined through the subsequent measurements of the skin-friction distributions on a circular cylinder (including the removal and bonding of the calibrated MHFS from a 10-cm diameter calibration cylinder and onto the surface of a 8-cm diameter test cylinder) and comparison of their consistency with the published results. The present MHFS calibration method is important in the non-intrusive multipoint measurements of the mean skin friction along the surfaces of two-dimensional aerodynamic objects of interest.

A case of traumatic rotatory dislocation associated with odontoid fracture is reported.

Benign neurogenic tumours originating from lumbar plexus or roots are rare. Two cases are reported. Resection, often possible with another localisation, may result in neurological deficit in these cases. Enucleation, the best choice, is not always feasible. Hollowing-out is therefore a procedure worth understanding.

Abstract: In order to contribute to a better understanding of the dispersion of cystic fibrosis (CF) mutations in the South of France, seven diallelic and three multiallelic markers [three upstream of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (XV-2c, KM.19 and J44) and seven intragenic polymorphisms (IVS6A, IVS8CA, M470V, T854T, IVS17BTA, IVS17BCA and TUB18)] were analyzed for 143 ΔF508 chromosomes, 100 CF chromosomes carrying 85 non-ΔF508 and 15 unknown mutations, and 198 normal CFTR alleles. The study provides haplotypic data for 39 different CF mutations, which should be useful in diagnosis by haplotypic analysis and detection of the associated mutations. A major haplotype [2-1-2-7-16-2-1-(30/31)-13-1] was found in normal chromosomes, which should be the most ancient in the Caucasoid population. The most frequent haplotypes in normal chromosomes were associated with 16 different non-ΔF508 mutations, suggesting that there was no preferential haplotype on which these mutations arose. Several mutations were each associated with more than one haplotype, as the result of slippage at one or two of the three microsatellites (ΔF508, G542X, N1303K, G85E, E585X, K710X and 2184delA) or recombination (1717-1G→A, R334W, L206W, R1162X and Y122X). Haplotypes for the most common CFTR mutations (ΔF508, G542X, N1303K) revealed that a large number of alleles were generated by slippage at the microsatellite loci, suggesting that they are the most ancient CF mutations. Other mutations were associated with haplotypes that were different either at several diallelic sites (R334W) or at both diallelic and microsatellite markers (R1162X and R1158X), which is more suggestive of recurrence. Twenty recombinations were detected among the CF mutant alleles analyzed, 75% of them occurring in the second half of the CFTR gene. The higher mutational heterogeneity and the haplotypic variability reported in this small population from the Mediterranean area are consistent with an earlier appearance of CFTR mutations in southern Europe than in central and northern Europe, and an earlier origin and expansion of this population.

Abstract: mRNA transcripts of the cystic fibrosis transmembrane conductance regulator (CFTR) gene were analyzed from lymphocytes of two cystic fibrosis compound heterozygotes (394delTT/3195del6 and 1215delG/ 2423delG), of five related carriers heterozygous for one of these mutations, and of five normal individuals. After reverse transcription of total RNA and amplification by the polymerase chain reaction, fragments were investigated by sequencing and by the protein truncation test (PTT). The three frameshift mutants were correctly detected by PTT, as they introduced a premature termination codon resulting in shortened protein products. The PTT approach thus provides a simple and reliable alternative method for detecting frameshift, nonsense, or splice site mutations, and for ascertaining their putative effect on the reading frame of the mRNA. In addition, we have identified 6 alternatively spliced forms of CFTR mRNA, two of which (transcripts lacking 4+5 or 17B) have not been described previously.

Several recent studies have demonstrated the presence of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in healthy males with infertility caused by congenital absence of the vas deferens (CBAVD), previously recognized as an idiopathic genetic condition distinct from CF. In order to document further the genetic commonality of these two disorders, we undertook a double screening of the entire coding and flanking sequences of the CFTR gene, by using single-strand conformational polymorphism analysis and denaturing gradient gel electrophoresis in 12 unrelated infertile men with abnormalities of the vas deferens and/or epididymis. This strategy allowed us to identify 11 DNA sequence alterations considered as CF-causing mutations and several variations. Despite this double analysis, only two patients out of eight with CBAVD could be demonstrated as compound heterozygotes for CF mutations.

Abstract: Cystic fibrosis (CF) is thought to be rare among the Arab populations from the Middle East and little data have been reported so far. We have studied a sample of 20 families living in Lebanon for several generations and who have at least one child with CF. These families are mainly from the Maronite, Greek Catholic, Greek Orthodox, Shiite or Sunnite groups. We found a 50% rate of consanguineous marriage, independent of the community of origin. The distribution of CF genotypes was determined through the screening of all exons of the CFTR (cystic fibrosis transmembrane conductance regulator) gene by the technique of denaturing gradient gel electrophoresis combined with asymmetric amplification DNA sequencing. A total of ten different mutations accounting for 87.5% of 32 unrelated CF alleles was identified, including two novel putative mutations (E672del and IVS21-28G→A). Three mutations, ΔF508 (37.5%), W1282X (15.6%), and N1303K (9.4%) accounted for 62.5% of CF alleles. Interestingly, in the Maronite group, 66.7% of the ΔF508 chromosomes were found to be associated with allele 7 of the IVS8(T)tract, contrasting with the absolute linkage disequilibrium between European ΔF508 chromosomes and allele 9. During this study, two previously undescribed polymorphisms (IVS14a + 17del5 and 2691T/C) were also identified.

ΔF508 is the most frequent cystic fibrosis (CF) mutation and accounts for approximately 70% of CF chromosomes worldwide. Three highly polymorphic microsatellite markers have been used to study the origin and evolution of ΔF508 chromosomes in Europe. Haplotype data demonstrate that ΔF508 occurred more than 52,000 years ago, in a population genetically distinct from any present European group, and spread throughout Europe in chronologically distinct expansions, which are responsible for the different frequencies of ΔF508 in Europe.

To define the potential role of interleukin-6 (IL-6) and its soluble receptor alpha in cartilage metabolism, we analyzed their effects on tissue inhibitor of metalloproteases (TIMP) synthesis by synoviocytes and chondrocytes. TIMP-1 production by isolated human articular synovial fibroblasts and chondrocytes, stimulated by IL-6 and/or its soluble receptor, was first assayed by specific enzyme-linked immunosorbent assay; the slight stimulatory effect of IL-6 on TIMP-1 production by both types of cells was markedly amplified by the addition of soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA expression, determined by ribonuclease protection assay, was induced by IL-6 together with its soluble receptor, but TIMP-2 and -3 mRNAs were not affected by these factors. A specific neutralizing antibody abolished the effects of the soluble receptor. Finally, supernatant from synoviocytes stimulated by IL-6 plus its soluble receptor blocked almost completely the collagenolytic activity of supernatant from IL-1-induced synoviocytes. These observations indicate that IL-6 and its soluble receptor have a protective role in the metabolism of cartilage. Given the high levels of soluble receptor in synovial fluid and the marked induction of IL-6 by IL-1 or TNF-alpha, it is likely that IL-6 and its soluble receptor are critical in controlling the catabolic effects of pro-inflammatory cytokines.

To define the potential role of interleukin-6 (IL-6) and its soluble receptor α in cartilage metabolism, we analyzed their effects on tissue inhibitor of metalloproteases (TIMP) synthesis by synoviocytes and chondrocytes. TIMP-1 production by isolated human articular synovial fibroblasts and chondrocytes, stimulated by IL-6 and/or its soluble receptor, was first assayed by specific enzyme-linked immunosorbent assay; the slight stimulatory effect of IL-6 on TIMP-1 production by both types of cells was markedly amplified by the addition of soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA expression, determined by ribonuclease protection assay, was induced by IL-6 together with its soluble receptor, but TIMP-2 and -3 mRNAs were not affected by these factors. A specific neutralizing antibody abolished the effects of the soluble receptor. Finally, supernatant from synoviocytes stimulated by IL-6 plus its soluble receptor blocked almost completely the collagenolytic activity of supernatant from IL-1-induced synoviocytes. These observations indicate that IL-6 and its soluble receptor have a protective role in the metabolism of cartilage. Given the high levels of soluble receptor in synovial fluid and the marked induction of IL-6 by IL-1 or TNF-α, it is likely that IL-6 and its soluble receptor are critical in controlling the catabolic effects of pro-inflammatory cytokines.

We report molecular and clinical analyses in four unrelated patients with cystic fibrosis (CF) with compound heterozygosity for the L206W mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). This uncommon missense mutation (frequency less than 1% in a sample of 336 CF chromosomes from Southern France) replaces a leucine by a tryptophan residue in the middle of the third transmembrane domain of CFTR. On the basis of the clinical features presented by the four patients, we postulate that the L206W might be associated with pancreatic sufficiency and residual transmembrane transport of chloride in lung.

Both perceived and objectively-measured attributes of the built environment have been related to active transport. They do not refer, however, to the same construct: objective measurements provide an inventory of a neighborhood's active-friendly attributes, while the perceptions of individuals refer to their appraisal of their neighborhood opportunities for active travel. Both aspects are complementary in explaining active transport. This study examines the independent associations of perceived and objective environmental attributes with active transport, and whether perceptions moderate the objectively-measured environment active transport relationship.

We have analyzed 131 unrelated families from Southern France for 29 known cystic fibrosis (CF) mutations identified in 8 exons of the cystic fibrosis transmembrane regulator gene. All these mutations were detected by amplification of DNA by the polymerase chain reaction (PCR) followed by restriction enzyme digestion or hybridization with allele specific oligoprobes. The most frequent mutations after the ΔF508 deletion (frequency: 63%) were G542X (5.3%), AI507 (1.1%), and N1303K (0.76%). Seven other mutations (621 + 1G → T, Y122X, R347P, R334W, S549N, G551D, R1162X) were each identified in only one CF chromosome. Apart from G542X, most of the other mutations identified in this study were found to be associated with 7-(GATT)-repeats allele of IVS6A. In Southern France, only 73% of CF chromosomes could be identified by the analysis of 30 mutations.

We have identified a Duchenne muscular dystrophy (DMD) pedigree with an unexpected pattern of inheritance. Using marker restriction fragment length polymorphisms detected by probes that lie within and outside the DMD gene, we could demonstrate that the maternal grandfather has transmitted two distinct types of X chromosomes to his offspring. This original observation may be explained by postulating that the DMD mutation must have occurred during mitosis in early germline proliferation, leading to a germline mosaicism within this male ancestor.

Congenital bilateral absence of the vas deferens (CBAVD) is a cause of male sterility mostly resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. The most common defect is the 5T variant at the branch/acceptor site of intron 8, which induces high levels of exon 9 skipping leading to non-functional protein. However, this 5T variant has incomplete penetrance and variable expressivity, suggesting that some other regulatory factors may modulate the splicing of exon 9. To identify such factors, we report here the genetic analysis of a polymorphic locus, M470V, located in exon 10 of the CFTR gene in 60 patients with CBAVD, compared to a normal control population. The statistical analysis showed strong linkage disequilibrium between the 5T allele and the V allele of the M470V polymorphism in the CBAVD population, but not in the normal population. The V allele in a gene carrying 5T could, however, contribute to lowering the level of normal transcripts, as already suggested by in vitro transcriptional studies. These genetic findings, together with previous studies, suggest involvement of the M470V variant in the modulation of the splicing of exon 9 of the CFTR gene.

Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in, virtually, all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments. The structures also differ among species, partly in the size and arrangement of these expansion segments. Such differences are extreme in kinetoplastids. Here, we present a high-resolution (∼5 Å) cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that which causes African Sleeping Sickness. The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large eukaryotic expansion segments and ribosomal protein extensions leading to the formation of four additional inter-subunit bridges. We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes. Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit rRNA chain, which is known to be cleaved uniquely into six pieces and suggests that the cleavage is important for the maintenance of the T. bruceiribosome in the observed structure. We discuss several possible implications of the large rRNA expansion segments for the translation regulation process, and we show a possible link between the protein translation initiation process and expansion segments 6 and 7 on the small ribosomal subunit. Our structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs.

Several letters to the editor are presented in response to articles in previous issues including features on blues musicians Johnny Winter and Matt Schofield and reggae artist Corey Harris.

Summary: A sample of 235 individuals from 49 French cystic fibrosis (CF) families with at least one living affected child was typed with probes for restriction fragment length polymorphisms (RFLPs) known to be linked to the CF gene, and was screened for the ΔF508 mutation. Using a combination of six probes, 44 out of the 49 families were sufficiently informative to enable prenatal diagnosis or carrier determination. As in many other populations, linkage disequilibrium was found between the CF locus and the haplotype B (XV2c: allele 1; KM19: allele 2), which accounts for about 78% of CF chromosomes in our families. The ΔF508 deletion was present in 64.3% of CF chromosomes.

A low cost and low temperature microelectromechanical systems (MEMS) transfer process is presented. The process is based on adhesion control of molded electroplated Ni microstructures on the donor wafer by using a plasma deposited fluorocarbon film. Adhesive bonding of the microstructures on the target wafer using BCB sealing enables mechanical tearing off from the donor wafer. This proposed process has allowed us to realize from 7 μm down to 700 nm thick Ni patterns on Si, Pyrex glass wafers and Kapton foils. Multiple transfers lead to Ni stacked microstructures. We demonstrated the interest of a simple film transfer process for the elaboration of 3D microstructures.

A low cost and low temperature MEMS transfer process is presented. The process is based on adhesion control of molded electroplated Ni microstructures on donor wafer by using plasma deposited fluorocarbon film. Adhesive bonding of the microstructures on the target wafer using BCB sealing enables mechanical tearing out from the donor wafer. This proposed process has allowed us to realize from 7 µm down to 700 nm thick Ni patterns on Si, Pyrex glass wafers and Kapton foils. Multiple transfers lead to Ni stacked microstructures. Because this process is simple and only involves a low temperature (250°C) heating of the host wafer, it is highly versatile and suitable for various applications and brings new perspectives towards 3D integration of MEMS/NEMS.