Mobile Robots for In-Process Monitoring of Aircraft Systems Assemblies.

Currently, systems installed on large-scale aerospace structures are manually equipped by trained operators. To improve current methods, an automated system that ensures quality control and process adherence could be used. This work presents a mobile robot capable of autonomously inspecting aircraft systems and providing feedback to workers. The mobile robot can follow operators and localise the position of the inspection using a thermal camera and 2D lidars. While moving, a depth camera collects 3D data about the system being installed. The in-process monitoring algorithm uses this information to check if the system has been correctly installed. Finally, based on these measurements, indications are shown on a screen to provide feedback to the workers. The performance of this solution has been validated in a laboratory environment, replicating a trailing edge equipping task. During testing, the tracking and localisation systems have proven to be reliable. The in-process monitoring system was also found to provide accurate feedback to the operators. Overall, the results show that the solution is promising for industrial applications.

Hepatitis B virus sub-genotype A1 infection is characterized by high replication levels and rapid emergence of drug resistance in HIV-positive adults receiving first-line antiretroviral therapy in Malawi.

BACKGROUND: It has been proposed that hepatitis B virus (HBV) sub-genotype A1 infections have mild outcomes and a low risk of drug-resistance among patients infected with human immunodeficiency virus (HIV) receiving lamivudine-containing antiretroviral therapy (ART) without tenofovir in Africa. METHODS: The virologic expression of HBV sub-genotype A1 coinfection was studied over 12 months in HIV-positive adults starting stavudine/lamivudine/nevirapine in Malawi, using Sanger, deep, clonal, and single full-genome sequencing for the sensitive characterization of HBV resistance-associated mutations (RAMs). RESULTS: Among 1117 subjects, 133 (12%) tested HBsAg-positive. After starting ART, retention rates were 96/133 (72%) at 6 months and 54/133 (41%) at 12 months. Based upon the last available follow-up, 92/96 (96%) subjects achieved HIV-1 RNA <40 copies/mL, 48/96 (50%) showed HBV DNA <14 IU/mL, and 24/96 (25%) acquired HBV RAMs. At 6 months, M204I was detected in 8/46 (17%) and 16/17 (94%) subjects using Sanger and deep sequencing, respectively. At 12 months, all viremic patients had multiple resistance and compensatory mutations coexisting on the same HBV genomes. Comparing HBeA-positive (67/133, 50%) with HBeAg-negative subjects, 64/67 (96%) vs 35/66 (55%) showed baseline HBV DNA >2000 IU/mL (P = .0006), 39/47 (17%) vs 9/49 (82%) had persistent HBV DNA detection during follow-up (P < .0001), and 23/47 (49%) vs 2/49 (4%) acquired HBV RAMs (P < .0001). Baseline HBV DNA levels were median 8.1 vs 5.3 log10 IU/mL in subjects with vs those without treatment-emergent RAMs (P < .0001). CONCLUSIONS: HBV sub-genotype A1 infections showed a severe virologic expression in HIV-positive Malawians. The findings strengthen the urgency of interventions to improve ascertainment and management of chronic hepatitis B in the region.

Microarray and deep sequencing cross-platform analysis of the mirRNome and isomiR variation in response to epidermal growth factor.

BACKGROUND: Epidermal Growth Factor (EGF) plays an important function in the regulation of cell growth, proliferation, and differentiation by binding to its receptor (EGFR) and providing cancer cells with increased survival responsiveness. Signal transduction carried out by EGF has been extensively studied at both transcriptional and post-transcriptional levels. Little is known about the involvement of microRNAs (miRNAs) in the EGF signaling pathway. miRNAs have emerged as major players in the complex networks of gene regulation, and cancer miRNA expression studies have evidenced a direct involvement of miRNAs in cancer progression. RESULTS: In this study, we have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by reverse transcription quantitative PCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomiRs) among regulated miRNAs. CONCLUSIONS: We propose that the use of global genomic miRNA cross-validation derived from high throughput technologies can be used to generate more reliable datasets inferring more robust networks of co-regulated predicted miRNA target genes.

HLA class I protective alleles in an HIV-1-infected subject homozygous for CCR5-Δ32/Δ32.

Homozygosity for a 32 bp deletion in CCR5 (CCR5-Δ32/Δ32) is associated with strong resistance against HIV-1 infection. Several HLA types have been associated to improved viral control and/or delayed progression to AIDS. We report a unique HIV-1 infected individual homozygous for CCR5-Δ32/Δ32 and carrier of HLA-A*2402 and HLA-B*5701. In comparison with earlier data and although a replication competent virus has been isolated, the patient presents better immune status, response to treatment and disease evolution, which may be related to the control exerted by HLA class I restricted T cell immunity. Importantly, the accumulation of protective factors does not warrant a complete protection to HIV infection and the subsequent life-long treatment.

MacroH2A1 regulates the balance between self-renewal and differentiation commitment in embryonic and adult stem cells.

One of the most striking epigenetic alterations that occurs at the level of the nucleosome is the complete exchange of the canonical H2A histones for the macroH2A variant. Here, we provide insight into the poorly recognized function of macroH2A in transcriptional activation and demonstrate its relevance in embryonic and adult stem cells. Knockdown of macroH2A1 in mouse embryonic stem (mES) cells limited their capacity to differentiate but not their self-renewal. The loss of macroH2A1 interfered with the proper activation of differentiation genes, most of which are direct target genes of macroH2A. Additionally, macroH2A1-deficient mES cells displayed incomplete inactivation of pluripotency genes and formed defective embryoid bodies. In vivo, macroH2A1-deficient teratomas contained a massive expansion of malignant, undifferentiated carcinoma tissue. In the heterogeneous culture of primary human keratinocytes, macroH2A1 levels negatively correlated with the self-renewal capacity of the pluripotent compartment. Together these results establish macroH2A1 as a critical chromatin component that regulates the delicate balance between self-renewal and differentiation of embryonic and adult stem cells.

Pt(II) coordination to N1 of 9-methylguanine: why it facilitates binding of additional metal ions to the purine ring.

The preparation and X-ray crystal structure analysis of {trans-[Pt(MeNH(2))(2)(9-MeG-N1)(2)]}⋅{3 K(2)[Pt(CN)(4)]}⋅6 H(2)O (3 a) (with 9-MeG being the anion of 9-methylguanine, 9-MeGH) are reported. The title compound was obtained by treating [Pt(dien)(9-MeGH-N7)](2+) (1; dien=diethylenetriamine) with trans-[Pt(MeNH(2))(2)(H(2)O)(2)](2+) at pH 9.6, 60 °C, and subsequent removal of the [(dien)Pt(II)] entities by treatment with an excess amount of KCN, which converts the latter to [Pt(CN)(4)](2-). Cocrystallization of K(2)[Pt(CN)(4)] with trans-[Pt(MeNH(2))(2)(9-MeG-N1)(2)] is a consequence of the increase in basicity of the guanine ligand following its deprotonation and Pt coordination at N1. This increase in basicity is reflected in the pK(a) values of trans-[Pt(MeNH(2))(2)(9-MeGH-N1)(2)](2+) (4.4±0.1 and 3.3±0.4). The crystal structure of 3 a reveals rare (N7,O6 chelate) and unconventional (N2,C2,N3) binding patterns of K(+) to the guaninato ligands. DFT calculations confirm that K(+) binding to the sugar edge of guanine for a N1-platinated guanine anion is a realistic option, thus ruling against a simple packing effect in the solid-state structure of 3 a. The linkage isomer of 3 a, trans-[Pt(MeNH(2))(2)(9-MeG-N7)(2)] (6 a) has likewise been isolated, and its acid-base properties determined. Compound 6 a is more basic than 3 a by more than 4 log units. Binding of metal entities to the N7 positions of 9-MeG in 3 a has been studied in detail for [(NH(3))(3)Pt(II)], trans-[(NH(3))(2)Pt(II)], and [(en)Pd(II)] (en=ethylenediamine) by using (1)H NMR spectroscopy. Without exception, binding of the second metal takes place at N7, but formation of a molecular guanine square with trans-[(Me(2)NH(2))Pt(II)] cross-linking N1 positions and trans-[(NH(3))(2)Pt(II)] cross-linking N7 positions could not be confirmed unambiguously, despite the fact that calculations are fully consistent with its existence.

Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis.

BACKGROUND: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer. RESULTS: By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We use this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we find an entirely new set of genes previously unrelated to the currently accepted EGF associated cellular functions. CONCLUSIONS: We propose that the use of global genomic cross-validation derived from high content technologies (microarrays or deep sequencing) can be used to generate more reliable datasets. This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data.

Cu2+/+ cation coordination to adenine--thymine base pair. Effects on intermolecular proton-transfer processes.

Intermolecular proton-transfer processes in the Watson & Crick adenine-thymine Cu+ and Cu2+ cationized base pairs have been studied using the density functional theory (DFT) methods. Cationized systems subject to study are those resulting from cation coordination to the main basic sites of the base pair, N7 and N3 of adenine and O2 of thymine. For Cu+ coordinated to N7 or N3 of adenine, only the double proton-transferred product is found to be stable, similarly to the neutral system. However, when Cu+ interacts with thymine, through the O2 carbonyl atom, the single proton transfer from thymine to adenine becomes thermodynamically spontaneous, and thus rare forms of the DNA bases may spontaneously appear. For Cu2+ cation, important effects on proton-transfer processes appear due to oxidation of the base pair, which stabilizes the different single proton-transfer products. Results for hydrated systems show that the presence of the water molecules interacting with the metal cation (and their mode of coordination) can strongly influence the ability of Cu2+ to induce oxidation on the base pair.