Routing Security in Mobile Ad-hoc Networks

The role of infrastructure-less mobile ad hoc networks (MANETs) in ubiquitous networks is outlined. In a MANET there are no dedicated routers and all network nodes must contribute to routing. Classification of routing protocols for MANET is based on how routing information is acquired and maintained by mobile nodes and/or on roles of network nodes in a routing. According to the first classification base, MANET routing protocols are proactive, reactive, or hybrid combinations of proactive and reactive protocols. According to the role-based classification, MANET routing protocols are either uniform when all network nodes have the same role or non-uniform when the roles are different and dedicated. A contemporary review of MANET routing protocols is briefly presented. Security attacks against MANET routing can be passive and or active. The purpose of the former is information retrieval, for example network traffic monitoring, while the latter is performed by malicious nodes with the express intention of disturbing, modifying or interrupting MANET routing. An overview of active attacks based on modification, impersonation/ spoofing, fabrication, wormhole, and selfish behavior is presented. The importance of cryptography and trust in secure MANET routing is also outlined, with relevant security extensions of existing routing protocols for MANETs described and assessed. A comparison of existing secure routing protocols form the main contribution in this paper, while some future research challenges in secure MANET routing are discussed

A Packet Traversal Time per Hop based Adaptive Wormhole Detection Algorithm for MANETs

Routing security challenges significantly impact the wide-scale adoption of mobile ad hoc networks (MANET), with wormholes constituting an especially severe threat. Wormhole detection algorithms like traversal time and hop count analysis (TTHCA) and modified transmission time-based mechanism (M-TTM) combine effective detection with low traffic overheads. TTHCA measures packet traversal time (PTT) per route hop count (HC), while M-TTM compares an expected round trip time (RTT) with a measured RTT. However, using only fixed thresholds for the permissible PTT/HC and measured RTT deviations respectively, both algorithms are compromised so participation mode (PM), out-of-band (O-B) wormholes are inadequately detected in MANETs with large radio range fluctuations. This paper presents an extended variant of the TTHCA algorithm called traversal time per hop analysis (TTpHA) that dynamically adapts the PTT per hop threshold to prevailing MANET conditions and nodes’ radio coverage. Experimental results confirm TTpHA provides superior PM O-B detection performance compared to TTHCA and M-TTM, with commensurately low false positive rates and traffic overheads

Production of genetically improved silver birch plantations in southern and central Sweden

Investing in planting genetically unproved silver birch (Betula pendula Roth) in Swedish plantations requires understanding how birch stands will develop over their entire rotation. Previous studies have indicated relatively low production of birch compared to Norway spruce (Picea abies (L.) Karst.) and Scots pine (Pinus sylvestris L.). This could result from using unrepresentative basic data, collected from unimproved, naturally-regenerated birch (Betula spp.) growing on inventory plots often located in coniferous stands. The objective of this study was to develop a basal area development function of improved silver birch and evaluate production over a full rotation period. We used data from 52 experiments including planted silver birch of different genetic breeding levels in southern and central Sweden. The experimental plots were established on fertile forest sites and on former agricultural lands, and were managed with different numbers of thinnings and basal area removal regimes. The model best describing total stand basal area development was a dynamic equation derived from the Korf base model. The analysis of the realized gain trial for birch showed a good stability of the early calculated relative differences in basal area between tested genotypes over time. Thus, the relative difference in basal area might be with cautious used as representation of the realized genetic gain. On average forest sites in southern Sweden, improved and planted silver birch could produce between 6-10.5 m(3) ha(-1) year(-1), while on fertile agriculture land the average productivity might be higher, especially with material coming from the improvement program. The performed analysis provided a first step toward predicting the effects of genetic improvement on total volume production and profitability of silver birch. However, more experiments arc needed to set up the relative differences between different improved material

A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125

The activity of RING ubiquitin ligases (E3s) depends on an interaction between the RING domain and ubiquitin conjugating enzymes (E2), but posttranslational events or additional structural elements, yet largely undefined, are frequently required to enhance or regulate activity. Here, we show for the ubiquitin ligase RNF125 that, in addition to the RING domain, a C2HC Zn finger (ZnF) is crucial for activity, and a short linker sequence (Li2(120-128)) enhances activity. The contribution of these regions was first shown with truncated proteins, and the essential role of the ZnF was confirmed with mutations at the Zn chelating Cys residues. Using NMR, we established that the C2HC ZnF/Li2(120-128) region is crucial for binding of the RING domain to the E2 UbcH5a. The partial X-ray structure of RNF125 revealed the presence of extensive intramolecular interactions between the RING and C2HC ZnF. A mutation at one of the contact residues in the C2HC ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Thus, we identified the structural basis for an essential role of the C2HC ZnF and conclude that this domain stabilizes the RING domain, and is therefore required for binding of RNF125 to an E2

Dissection of progenitor compartments resolves developmental trajectories in B-lymphopoiesis

To understand the developmental trajectories in early lymphocyte differentiation, we identified differentially expressed surface markers on lineage-negative lymphoid progenitors (LPs). Single-cell polymerase chain reaction experiments allowed us to link surface marker expression to that of lineage-associated transcription factors (TFs) and identify GFRA2 and BST1 as markers of early B cells. Functional analyses in vitro and in vivo as well as single-cell gene expression analyses supported that surface expression of these proteins defined distinct subpopulations that include cells from both the classical common LPs (CLPs) and Fraction A compartments. The formation of the GFRA2-expressing stages of development depended on the TF EBF1, critical both for the activation of stage-specific target genes and modulation of the epigenetic landscape. Our data show that consecutive expression of Ly6D, GFRA2, and BST1 defines a developmental trajectory linking the CLP to the CD19(+) progenitor compartment.Peer reviewe

Integration of molecular profiles in a longitudinal wellness profiling cohort

An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine

Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model

Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinol, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia

The human secretome

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood

Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe