Design and development of a mobile robotic system for aircraft wing fuel tank inspection

This paper presents the design concept behind a novel remote visual inspection robotic system for fighter jet aircraft wing fuel tank inspection. This work is part of a larger research project which focuses on design, simulation, physical prototyping and experimental validation of a robotic system. Whereas this paper specifically focuses on the development concept of locomotion design choice for the robot. Therefore without an effective mobility method the robot will not be able to fulfill its purpose to access the hazardous confined spaces of the fuel tank. Aircraft wing fuel tank inspection is a challenging area of maintenance which requires a considerable amount of preparation and involvement of several tasks in order to conduct effective Visual and Non Destructive Inspection. The environment of an aircraft wing fuel tank poses several challenges due to both physical and atmospheric constraints which can be detrimental to human personal. This paper introduces an effective locomotion design which should allow the robot to enter and maneuver within confined spaces. The robot is relatively small, approximately 70mm in height and width yet, flexible enough to move within the restricted spaces of the wing. The mobile robot platform is a combination of small track systems that articulate like a snake. An additional mobile platform deploys an inspection sensor to reach the spaces that are unreachable by the robot body. Like other proposed robotic systems this particular proposal differs as it allows the robot to enter from the root of the wing and reach the narrower spaces towards with the wing tip. This paper highlights the stakeholder requirements to illustrate the foundation of the robotic system design. An overview of current complications of wing fuel tank inspection is presented and the analysis of current proposed robotic systems for wing fuel tank inspection. An engineering design methodology approach is followed for this project. Several locomotion methods are evaluated and an innovative locomotion method is illustrated with the use of CAD models. The desired outcome of this research is to eliminate the entry or close contact with the fuel tank by human personal

Requirements for designing a robotic system for aircraft wing fuel tank inspection

This paper presents the requirements for a robotic system to carry out inspection of fighter aircraft wing fuel tank, typical of challenging harsh environment. The research investigates the challenging case of fighter aircraft wing tank inspection. The wing shape geometry is highly irregular with very few fixed cartesian reference points. The internal structure is congested with many systems and difficult to manoeuvre within. This paper summarizes the key requirements for inspection robotics for fighter aircraft wing tank inspection. The requirements are presented in three categories; i) Robotic locomotion and navigation imposed by the complex and confined space inside the wing structure, ii) the materials, mechanisms and power sources imposed by the hazardous and potentially explosive environment inside the wing tank and lastly, iii) the inspection sensors and assessment algorithms to detect fuel tank defect and degradation features. The authors focus on the flexibility and mobility challenges to overcome the numerous obstacles within the confined space whilst effectively integrating a visual inspection technique to capture defined defects. The paper starts with an overview of existing maintenance practices, highlighting the implications and challenges of these methods. Their limitations inspire the development of novel robotics to achieve detailed internal inspection of an aircraft wing fuel tank. A design concept is proposed together with the validation test methods

Survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition

<p>Abstract</p> <p>Background</p> <p>Prostate cancer is a leading cause of cancer-related death in men worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) protein family that is expressed in the majority of human tumors including prostate cancer, but is barely detectable in terminally differentiated normal cells. Downregulation of survivin could sensitize prostate cancer cells to chemotherapeutic agents <it>in vitro </it>and <it>in vivo</it>. Selenium is an essential trace element. Several studies have shown that selenium compounds inhibit the growth of prostate cancer cells. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the underlying mechanisms.</p> <p>Methods</p> <p>Expression of survivin was analyzed in a collection of normal and malignant prostatic tissues by immunohistochemical staining. <it>In vitro </it>studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The effect of selenium on survivin expression was analyzed by Western blotting and semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting cells with a short hairpin RNA (shRNA) designed against survivin. Cell proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)- 2,5-Diphenyltetrazolium Bromide (MTT) assay and apoptosis by propidium iodide staining followed by flow cytometry analysis. Finally, <it>in vivo </it>tumor growth assay was performed by establishing PC-3M xenograft in nude mice and monitoring tumor growth following transfection and treatment.</p> <p>Results</p> <p>We found that survivin was undetectable in normal prostatic tissues but was highly expressed in prostate cancers. Survivin knockdown or selenium treatment inhibited the growth of prostate cancer cells, but the selenium effect was modest. In contrast to what have been observed in other cell lines, selenium treatment had little or no effect on survivin expression in several androgen-independent prostate cancer cell lines. Survivin knockdown sensitized these cells to selenium growth inhibition and apoptosis induction. In nude mice bearing PC-3M xenografts, survivin knockdown synergizes with selenium in inhibiting tumor growth.</p> <p>Conclusions</p> <p>Selenium could inhibit the growth of hormone-refractory prostate cancer cells both <it>in vitro </it>and <it>in vivo</it>, but the effects were modest. The growth inhibition was not mediated by downregulating survivin expression. Survivin silencing greatly enhanced the growth inhibitory effects of selenium.</p

Advances in ophthalmic drug delivery

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient’s lifetime

Effectiveness of ophthalmic solution preservatives: a comparison of latanoprost with 0.02% benzalkonium chloride and travoprost with the sofZia preservative system

<p>Abstract</p> <p>Background</p> <p>Although in vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK. Despite the conflicting evidence, BAK is the most commonly used preservative in ophthalmic products largely due to its proven antimicrobial efficacy. This study was designed to characterize the antimicrobial performance of two commonly used topical ocular hypotensive agents that employ different preservative systems: latanoprost 0.005% with 0.02% BAK and travoprost 0.004% with sofZia, a proprietary ionic buffer system.</p> <p>Methods</p> <p>Each product was tested for antimicrobial effectiveness by <it>European Pharmacopoeia </it>A (EP-A) standards, the most stringent standards of the three major compendia, which specify two early sampling time points (6 and 24 hours) not required by the <it>United States Pharmacopeia </it>or <it>Japanese Pharmacopoeia</it>. Aliquots were inoculated with between 10⁵and 10⁶colony-forming units of the test organisms: <it>Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans </it>and <it>Aspergillus brasiliensis</it>. Sampling and enumeration were conducted at protocol-defined time points through 28 days.</p> <p>Results</p> <p>BAK-containing latanoprost met EP-A criteria by immediately reducing all bacterial challenge organisms to the test sensitivity and fungal challenges within the first six hours while the preservative activity of travoprost with sofZia did not. Complete bacterial reduction by travoprost with sofZia was not shown until seven days into the test, and fungal reduction never exceeded the requisite 2 logs during the 28-day test. Travoprost with sofZia also did not meet EP-B criteria due to its limited effectiveness against <it>Staphylococcus aureus</it>. Both products satisfied United States and Japanese pharmacopoeial criteria.</p> <p>Conclusions</p> <p>Latanoprost with 0.02% BAK exhibited more effective microbial protection than travoprost with sofZia using rates of microbial reduction, time to no recovery for all challenges and evaluation against EP-A criteria as measures. The rapid and complete reduction of all microbial challenges demonstrates that antimicrobial activity of latanoprost with 0.02% BAK exceeds that of travoprost with sofZia preservative system in these products and provides a more protective environment in the event of contamination and subsequent exposure to microorganisms during use.</p

Monitoring lactoferrin iron levels by fluorescence resonance energy transfer: A combined chemical and computational study

Three forms of lactoferrin (Lf) that differed in their levels of iron loading (Lf, LfFe, and LfFe2) were simultaneously labeled with the fluorophores AF350 and AF430. All three resulting fluorescent lactoferrins exhibited fluorescence resonance energy transfer (FRET), but they all presented different FRET patterns. Whereas only partial FRET was observed for Lf and LfFe, practically complete FRET was seen for the holo form (LfFe2). For each form of metal-loaded lactoferrin, the AF350–AF430 distance varied depending on the protein conformation, which in turn depended on the level of iron loading. Thus, the FRET patterns of these lactoferrins were found to correlate with their iron loading levels. In order to gain greater insight into the number of fluorophores and the different FRET patterns observed (i.e., their iron levels), a computational analysis was performed. The results highlighted a number of lysines that have the greatest influence on the FRET profile. Moreover, despite the lack of an X-ray structure for any LfFe species, our study also showed that this species presents modified subdomain organization of the N-lobe, which narrows its iron-binding site. Complete domain rearrangement occurs during the LfFe to LfFe2 transition. Finally, as an example of the possible applications of the results of this study, we made use of the FRET fingerprints of these fluorescent lactoferrins to monitor the interaction of lactoferrin with a healthy bacterium, namely Bifidobacterium breve. This latter study demonstrated that lactoferrin supplies iron to this bacterium, and suggested that this process occurs with no protein internalization.This work was supported by MINECO and FEDER (projects CTQ2012-32236, CTQ2011-23336, and BIO2012-39682-C02-02) and BIOSEARCH SA. F.C. and V.M.R. are grateful to the Spanish MINECO for FPI fellowships

Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes

BACKGROUND: The cystic fibrosis (CF) mouse pancreas has constitutively elevated expression of the Reg/PAP cell stress genes (60-fold greater Reg3α, and 10-fold greater PAP/Reg3β and Reg3γ). These genes are suggested to be involved in protection or recovery from pancreatic injury. METHODS: To test this idea the supramaximal caerulein model was used to induce acute pancreatitis in wild type and CF mice. Serum amylase, pancreatic water content (as a measure of edema), pancreatic myeloperoxidase activity, and Reg/PAP expression were quantified. RESULTS: In both wild type and CF mice caerulein induced similar elevations in serum amylase (maximal at 12 h), pancreatic edema (maximal at 7 h), and pancreatic myeloperoxidase activity (MPO, a marker of neutrophil infiltration; maximal at 7 h). By immunohistochemistry, Reg3α was strongly expressed in the untreated CF pancreas but not in wild type. During pancreatitis, Reg3α was intensely expressed in foci of inflamed tissue in both wild type and CF. CONCLUSION: These data demonstrate that the severity of caerulein-induced pancreatitis is not ameliorated in the CF mouse even though the Reg/PAP stress genes are already highly upregulated. While Reg/PAP may be protective they may also have a negative effect during pancreatitis due to their anti-apoptotic activity, which has been shown to increase the severity of pancreatitis

REST is a hypoxia-responsive transcriptional repressor

Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia