Damage tolerance analysis for Blackshape BS 115 programme, EASA CS VLA & CS-23

The thesis project has been developed in partnership with the Design Department of Blackshape Spa, a carbon – fiber ultra – light airplane company in Monopoli (Bari, Italy). The main goal is the assessment of a starting point for a damage tolerant concept during the design and certification phases of the Blackshape BS 115 airplane, with respect to EASA CS VLA & CS 23 Regulations. This approach has been carried out starting from an initial literary review as far as the way of modeling composites fractures is concerned. Further on, three finite element models have been generated and implemented in order to simulate defects occurring during manufacturing and service phases. At last, the procedures of non - destructive inspections have been taken into account, in order to establish how to investigate primary structures defects and delaminations during maintenance.

Analysis and mapping of CACNB4, CHRNA1, KCNJ3, SCN2A and SPG4, physiological candidate genes for porcine congenital progressive ataxia and spastic paresis

The cause of porcine congenital progressive ataxia and spastic paresis (CPA) is unknown. This severe neuropathy manifests shortly after birth and is lethal. The disease is inherited as a single autosomal recessive allele, designated cpa. In a previous study, we demonstrated close linkage of cpa to microsatellite SW902 on porcine chromosome 3 (SSC3), which corresponds syntenically to human chromosome 2. This latter chromosome contains ion channel genes (Ca(2+), K(+) and Na(+)), a cholinergic receptor gene and the spastin (SPG4) gene, which cause human epilepsy and ataxia when mutated. We mapped porcine CACNB4, KCNJ3, SCN2A and CHRNA1 to SSC15 and SPG4 to SSC3 with the INRA-Minnesota porcine radiation hybrid panel (IMpRH) and we sequenced the entire open reading frames of CACNB4 and SPG4 without finding any differences between healthy and affected piglets. An anti-epileptic drug treatment with ethosuximide did not change the severity of the disease, and pigs with CPA did not exhibit the corticospinal tract axonal degeneration found in humans suffering from hereditary spastic paraplegia, which is associated with mutations in SPG4. For all these reasons, the hypothesis that CACNB4, CHRNA1, KCNJ3, SCN2A or SPG4 are identical with the CPA gene was rejected.

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma

AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage.

AN ANALYSIS OF THE DNA DAMAGE INDUCED BY NICKEL COMPOUNDS IN CHINESE HAMSTER OVARY CELLS (CARCINOGENESIS, HETEROCHROMATIN, CYTOTOXICITY, REPLICATION, PROTEIN CROSSLINKING)

The carcinogenic activity of water-insoluble crystalline nickel sulfide requires phagocytosis and lysosome-mediated intracellular dissolution of the particles to yield Ni('2+). This study investigated the extent and nature of the DNA damage in Chinese hamster ovary cells treated with various nickel compounds using the technique of alkaline elution. Crystalline NiS and water-soluble NiCl(,2) induced single strand breaks that were repaired quickly and DNA-protein crosslinks that persisted up to 24 hr after exposure to nickel. The induction of single strand breaks was concentration dependent at both noncytotoxic and lethal amounts of nickel. The induction of DNA-protein crosslinks was concentration dependent but was absent at lethal amounts of nickel. The cytoplasmic and nuclear uptake of nickel was concentration dependent even at the toxic level of nickel. However, the induction of DNA-protein crosslinks by nickel required active cell cycling and occurred predominantly in mid-late S phase of the cell cycle, suggesting that the lethal amounts of nickel inhibited DNA-protein crosslinking by inhibiting active cell cycling. Since the DNA-protein crosslinking induced by nickel was resistant to DNA repair, the nature of this lesion was investigated using various methods of DNA isolation and chromatin fractionation in combination with SDS-polyacrylamide gel electrophoresis. High molecular weight, non-histone chromosomal proteins and possibly histone 1 were preferentially crosslinked to DNA by nickel. The crosslinked proteins were concentrated in a magnesium-insoluble fraction of sonicated chromatin (5% of the total) that was similar to heterochromatin in solubility and protein composition. Alterations in DNA structure and function, brought about by the effect of nickel on protein-DNA interactions, may be related to the carcinogenicity of nickel compounds. ^

Understanding the roles of Non-homologous end joining and p53 after DNA damage

The inability to maintain genomic stability and control proliferation are hallmarks of many cancers, which become exacerbated in the presence of unrepaired DNA damage. Such genotoxic stresses trigger the p53 tumor suppressor network to activate transient cell cycle arrest allowing for DNA repair; if the damage is excessive or irreparable, apoptosis or cellular senescence is triggered. One of the major DNA repair pathway that mends DNA double strand breaks is non-homologous end joining (NHEJ). Abrogating the NHEJ pathway leads to an accumulation of DNA damage in the lymphoid system that triggers p53-mediated apoptosis; complete deletion of p53 in this system leads to aggressive lymphomagenesis. Therefore, to study the effect of p53-dependent cell cycle arrest, we utilized a hypomorphic, separation-of-function mutant, p53p/p, which completely abrogates apoptosis yet retains partial cell cycle arrest ability. We crossed DNA ligase IV deficiency, a downstream ligase crucial in mending breaks during NHEJ, into the p53p/p background (Lig4-/-p53p/p). The accumulation of DNA damage activated the p53/p21 axis to trigger cellular senescence in developing lymphoid cells, which absolutely suppressed tumorigenesis. Interestingly, these mice progressively succumb to severe diabetes. Mechanistic analysis revealed that spontaneous DNA damage accumulated in the pancreatic b-cells, a unique subset of endocrine cells solely responsible for insulin production to regulate glucose homeostasis. The genesis of adult b-cells predominantly occurs through self-replication, therefore modulating cellular proliferation is an essential component for renewal. The progressive accumulation of DNA damage, caused by Lig4-/-, activated p53/p21-dependent cellular senescence in mutant pancreatic b-cells that lead to islet involution. Insulin levels subsequently decreased, deregulating glucose homeostasis driving overt diabetes. Our Lig4-/-p53p/p model aptly depicts the dichotomous role of cellular senescence—in the lymphoid system prevents tumorigenesis yet in the endocrine system leads to the decrease of insulin-producing cells causing diabetes. To further delineate the function of NHEJ in pancreatic b-cells, we analyzed mice deficient in another component of the NHEJ pathway, Ku70. Although most notable for its role in DNA damage recognition and repair within the NHEJ pathway, Ku70 has NHEJ-independent functions in telomere maintenance, apoptosis, and transcriptional regulation/repression. To our surprise, Ku70-/-p53p/p mutant mice displayed a stark increase in b-cell proliferation, resulting in islet expansion, heightened insulin levels and hypoglycemia. Augmented b-cell proliferation was accompanied with the stabilization of the canonical Wnt pathway, responsible for this phenotype. Interestingly, the progressive onset of cellular senescence prevented islet tumorigenesis. This study highlights Ku70 as an important modulator in not only maintaining genomic stability through NHEJ-dependent functions, but also reveals a novel NHEJ-independent function through regulation of pancreatic b-cell proliferation. Taken in aggregate, these studies underscore the importance for NHEJ to maintain genomic stability in b-cells as well as introduces a novel regulator for pancreatic b-cell proliferation.

A robust procedure for damage detection from strain measurements based on principal component analysis

FBGs are excellent strain sensors, because of its low size and multiplexing capability. Tens to hundred of sensors may be embedded into a structure, as it has already been demonstrated. Nevertheless, they only afford strain measurements at local points, so unless the damage affects the strain readings in a distinguishable manner, damage will go undetected. This paper show the experimental results obtained on the wing of a UAV, instrumented with 32 FBGs, before and after small damages were introduced. The PCA algorithm was able to distinguish the damage cases, even for small cracks. Principal Component Analysis (PCA) is a technique of multivariable analysis to reduce a complex data set to a lower dimension and reveal some hidden patterns that underlie.

X-ray microtomography analysis of the damage micromechanisms in 3D woven composites under low-velocity impact

3D woven composites reinforced with either S2 glass, carbon or a hybrid combination of both and containing either polyethylene or carbon z-yarns were tested under low-velocity impact. Different impact energies (in the range of 21–316 J) were used and the mechanical response (in terms of the impact strength and energy dissipated) was compared with that measured in high-performance, albeit standard, 2D laminates. It was found that the impact strength in both 2D and 3D materials was mainly dependent on the in-plane fiber fracture. Conversely, the energy absorption capability was primarily influenced by the presence of z-yarns, having the 3D composites dissipated over twice the energy than the 2D laminates, irrespective of their individual characteristics (fiber type, compaction degree, porosity, etc.). X-ray microtomography revealed that this improvement was due to the z-yarns, which delayed delamination and maintained the structural integrity of the laminate, promoting energy dissipation by tow splitting, intensive fiber breakage under the tup and formation of a plug by out-of-plane shear.

Analysis of the influence of the different variables involved in a damage progression probability model

Motivated by these difficulties, Castillo et al. (2012) made some suggestions on how to build consistent stochastic models avoiding the selection of easy to use mathematical functions, which were replaced by those resulting from a set of properties to be satisfied by the model.

White matter damage disorganizes brain functional networks in amnestic mild cognitive impairment

Although progressive functional brain network disruption has been one of the hallmarks of Alzheimer?s Dis- ease, little is known about the origin of this functional impairment that underlies cognitive symptoms. We in- vestigated how the loss of white matter (WM) integrity disrupts the organization of the functional networks at different frequency bands. The analyses were performed in a sample of healthy elders and mild cognitive im- pairment (MCI) subjects. Spontaneous brain magnetic activity (measured with magnetoencephalography) was characterized with phase synchronization analysis, and graph theory was applied to the functional networks. We identified WM areas (using diffusion weighted magnetic resonance imaging) that showed a statistical de- pendence between the fractional anisotropy and the graph metrics. These regions are part of an episodic mem- ory network and were also related to cognitive functions. Our data support the hypothesis that disruption of the anatomical networks influences the organization at the functional level resulting in the prodromal dementia syndrome of MCI.

Analysis of the damage domains of sbo sequences with rcp passive thermal shutdown

The integrated Safety Assessment (ISA) methodology, developed by the Spanish Nuclear Safety Council (CSN), has been applied to a thermal-hydraulic analysis of PWR Station Blackout (SBO) sequences in the context of the IDPSA (Integrated Deterministic-Probabilistic Safety Assessment) network objectives. The ISA methodology allows obtaining the damage domain (the region of the uncertain parameters space where the damage limit is exceeded) for each sequence of interest as a function of the operator actuations times. Given a particular safety limit or damage limit, several data of every sequence are necessary in order to obtain the exceedance frequency of that limit. In this application these data are obtained from the results of the simulations performed with MAAP code transients inside each damage domain and the time-density probability distributions of the manual actions. Damage limits that have been taken into account within this analysis are: local cladding damage (PCT>1477 K); local fuel melting (T>2499 K); fuel relocation in lower plenum and vessel failure. Therefore, to every one of these damage variables corresponds a different damage domain. The operation of the new passive thermal shutdown seals developed by several companies since Fukushima accident is considered in the paper. The results show the capability and necessity of the ISA methodology, or similar, in order to obtain accurate results that take into account time uncertainties.

The cellular ecology of progressive neoplastic transformation: A clonal analysis

A comparison was made of the competence for neoplastic transformation in three different sublines of NIH 3T3 cells and multiple clonal derivatives of each. Over 90% of the neoplastic foci produced by an uncloned transformed (t-SA′) subline on a confluent background of nontransformed cells were of the dense, multilayered type, but about half of the t-SA′ clones produced only light foci in assays without background. This asymmetry apparently arose from the failure of the light focus formers to register on a background of nontransformed cells. Comparison was made of the capacity for confluence-mediated transformation between uncloned parental cultures and their clonal derivatives by using two nontransformed sublines, one of which was highly sensitive and the other relatively refractory to confluence-mediated transformation. Transformation was more frequent in the clones than in the uncloned parental cultures for both sublines. This was dramatically so in the refractory subline, where the uncloned culture showed no overt sign of transformation in serially repeated assays but increasing numbers of its clones exhibited progressive transformation. The reason for the greater susceptibility of the pure clones is apparently the suppression of transformation among the diverse membership that makes up the uncloned parental culture. Progressive selection toward increasing degrees of transformation in confluent cultures plays a major role in the development of dense focus formers, but direct induction by the constraint of confluence may contribute by heritably damaging cells. In view of our finding of increased susceptibility to transformation in clonal versus uncloned populations, expansion of some clones at the expense of others during the aging process would contribute to the marked increase of cancer with age.

Analysis of 1981 and 1982 insurance claims to determine effect of 1981 and 1982 bumpers on crash damage. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Analysis of insurance claims to determine bumper effect on crash damage. Final report.

National Highway Traffic Safety Administration, Office of Plans and Programs, Washington, D.C.

Analysis and forecast of truck traffic loads and the relative damage to pavement systems as a function of axle configurations. Final report.

Texas State Department of Highways and Public Transportation, Transportation Planning Division, Austin