A hybrid Particle Swarm Optimization - Simplex algorithm (PSOS) for structural damage identification

This study proposes a new PSOS-model based damage identification procedure using frequency domain data. The formulation of the objective function for the minimization problem is based on the Frequency Response Functions (FRFs) of the system. A novel strategy for the control of the Particle Swarm Optimization (PSO) parameters based on the Nelder-Mead algorithm (Simplex method) is presented; consequently, the convergence of the PSOS becomes independent of the heuristic constants and its stability and confidence are enhanced. The formulated hybrid method performs better in different benchmark functions than the Simulated Annealing (SA) and the basic PSO (PSO(b)). Two damage identification problems, taking into consideration the effects of noisy and incomplete data, were studied: first, a 10-bar truss and second, a cracked free-free beam, both modeled with finite elements. In these cases, the damage location and extent were successfully determined. Finally, a non-linear oscillator (Duffing oscillator) was identified by PSOS providing good results. (C) 2009 Elsevier Ltd. All rights reserved

A ductile damage criterion at various stress triaxialities

The paper discusses the effect of stress triaxiality on the onset and evolution of damage in ductile metals. A series of tests including shear tests and experiments oil smooth and pre-notched tension specimens wits carried Out for it wide range of stress triaxialities. The underlying continuum damage model is based oil kinematic definition of damage tensors. The modular structure of the approach is accomplished by the decomposition of strain rates into elastic, plastic and damage parts. Free energy functions with respect to fictitious undamaged configurations as well as damaged ones are introduced separately leading to elastic material laws which are affected by increasing damage. In addition, a macroscopic yield condition and a flow rule are used to adequately describe the plastic behavior. Numerical simulations of the experiments are performed and good correlation of tests and numerical results is achieved. Based oil experimental and numerical data the damage criterion formulated in stress space is quantified. Different branches of this function are taken into account corresponding to different damage modes depending oil stress triaxiality and Lode parameter. In addition, identification of material parameters is discussed ill detail. (C) 2007 Elsevier Ltd. All rights reserved.

Genetic interactions of the Ashergillus nidulans atmA(ATM) homolog with different components of the DNA damage response pathway

Ataxia telangiectasia mutated (ATM) is a phosphatidyl-3-kinase-related protein kinase that functions as a central regulator of the DNA damage response in eukaryotic cells. In humans, mutations in ATM cause the devastating neurodegenerative disease ataxia telangiectasia. Previously, we characterized the homolog of ATM (AtmA) in the filamentous fungus Aspergillus nidulans. In addition to its expected role in the DNA damage response, we found that AtmA is also required for polarized hyphal growth. Here, we extended these studies by investigating which components of the DNA damage response pathway are interacting with AtmA. The AtmA(ATM) loss of function caused synthetic lethality when combined with mutation in UvsB(ATR). Our results suggest that AtmA and UvsB are interacting and they are probably partially redundant in terms of DNA damage sensing and/or repairing and polar growth. We identified and inactivated A. nidulans chkA(CHK1) and chkB(CHK2) genes. These genes are also redundantly involved in A. nidulans DNA damage response. We constructed several combinations of double mutants for Delta atmA, Delta uvsB, Delta chkA, and Delta chkB. We observed a complex genetic relationship with these mutations during the DNA replication checkpoint and DNA damage response. Finally, we observed epistatic and synergistic interactions between AtmA, and bimE(APCI), ankA(WEE1) and the cdc2-related kinase npkA, at S-phase checkpoint and in response to DNA-damaging agents.

Treatment with a p38 MAPK inhibitor attenuates cisplatin nephrotoxicity starting after the beginning of renal damage

Aims: Cisplatin (CP) promotes increased production of reactive oxygen species, which can activate p38 mitogen activated protein kinases (p38 MAPKs) leading to apoptosis and increased expression of proinflammatory mediators that intensify the cytotoxic effects of CP. We investigated the effect of the treatment with S13203580, a p38 MAPKs inhibitor, on oxidative stress, on the oxidation-associated signal, p38 MAPK and on apoptosis in U-injected rats, starting after the beginning of the renal damage. Main methods: Rats (n = 21) were injected with CP (5 mg/kg, i.p.) and 3 and 4 days after some of them (n = 8) were treated with SB203580 (0.5 mg/kg, i.p.). Controls (n = 6) received saline (i.p.). Two or five days after saline or CP injections, plasma creatinine, urinary volume, sodium and potassium fractional excretions, blood urea nitrogen and urinary lipid peroxidation were measured. The kidneys were removed for histological, apoptosis, immunohistochemical and Western blot studies. Key findings: CP caused abnormalities in kidney functions and structure associated with raised urinary peroxidation levels and higher number of apoptotic cells in the outer medulla. The immunostaining studies showed increased numbers of macrophages/monocytes and p-p38 MAPKs positive cells in the renal outer medulla. The increase of p-p38 MAPKs expression was confirmed by Western blot analysis. All of these alterations were attenuated by treatment with S13203580. Significance: These data suggest that the beneficial effect of SB203580 on CP-induced renal damage might be related, in part, to the blockade of p38 MAPK activation with reduction of the inflammatory process, oxidative stress and apoptotic cell death. (C) 2009 Elsevier Inc. All rights reserved.

ATM, a central controller of cellular responses to DNA damage

Mutations in the ATM gene lead to the genetic disorder ataxia-telangiectasia. ATM encodes a protein kinase that is mainly distributed in the nucleus of proliferating cells. Recent studies reveal that ATM regulates multiple cell cycle checkpoints by phosphorylating different targets at different stages of the cell cycle. ATM also functions in the regulation of DNA repair and apoptosis, suggesting that it is a central regulator of responses to DNA double-strand breaks.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

Damage detection and quantification using transmissibility

Structures experience various types of loads along their lifetime, which can be either static or dynamic and may be associated to phenomena of corrosion and chemical attack, among others. As a consequence, different types of structural damage can be produced; the deteriorated structure may have its capacity affected, leading to excessive vibration problems or even possible failure. It is very important to develop methods that are able to simultaneously detect the existence of damage and to quantify its extent. In this paper the authors propose a method to detect and quantify structural damage, using response transmissibilities measured along the structure. Some numerical simulations are presented and a comparison is made with results using frequency response functions. Experimental tests are also undertaken to validate the proposed technique. (C) 2011 Elsevier Ltd. All rights reserved.

Damage detection in structures using a transmissibility-based Mahalanobis distance

In this paper, a damage-detection approach using the Mahalanobis distance with structural forced dynamic response data, in the form of transmissibility, is proposed. Transmissibility, as a damage-sensitive feature, varies in accordance with the damage level. Besides, Mahalanobis distance can distinguish the damaged structural state condition from the undamaged one by condensing the baseline data. For comparison reasons, the Mahalanobis distance results using transmissibility are compared with those using frequency response functions. The experiment results reveal quite a significant capacity for damage detection, and the comparison between the use of transmissibility and frequency response functions shows that, in both cases, the different damage scenarios could be well detected. Copyright (c) 2015 John Wiley & Sons, Ltd.

Novel functions of the cohesin accessory factor dPDS5 uncover a new meiotic checkpoint

Dissertation presented to obtain the Ph.D degree in Biology.

Effector functions of eosinophils in schistosomiasis

The dual function of eosinophils is clearly illustred in schistosomiasis. Well equipped in membrane receptors for immunoglobulins and complement, and due to the presence of granule basic proteins, eosinophils can become cytotoxic for parasite larvae and thus participate to protective immunity. However mediators can also exert their cytolytic effect on normal cells or tissues, inducing therefore pathology. Through ADCC mechanisms against schistosome larvae in vitro involving different antibody isotypes (IgG, IgE and IgA) and also in experiments performed in vivo, eosinophils have been clearly involved in protective immunity. Although no direct evidence of the protective role of eosinophils were brought in humans, the striking association of eosinophil-dependent cytotoxic antibody isotypes with resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, strongly, suggested the participation of eosinophils in antibody-dependent protective immune response. However eosinophils could also participate to granuloma formation around S. mansoni eggs and consequently to the pathological reactions induced by schistosomiasis.

E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases.

E2F1 is a key positive regulator of human cell proliferation and its activity is altered in essentially all human cancers. Deregulation of E2F1 leads to oncogenic DNA damage and anti-oncogenic apoptosis. The molecular mechanisms by which E2F1 mediates these two processes are poorly understood but are important for understanding cancer progression. During the G1-to-S phase transition, E2F1 associates through a short DHQY sequence with the cell-cycle regulator HCF-1 together with the mixed-lineage leukaemia (MLL) family of histone H3 lysine 4 (H3K4) methyltransferases. We show here that the DHQY HCF-1-binding sequence permits E2F1 to stimulate both DNA damage and apoptosis, and that HCF-1 and the MLL family of H3K4 methyltransferases have important functions in these processes. Thus, HCF-1 has a broader role in E2F1 function than appreciated earlier. Indeed, sequence changes in the E2F1 HCF-1-binding site can modulate both up and down the ability of E2F1 to induce apoptosis indicating that HCF-1 association with E2F1 is a regulator of E2F1-induced apoptosis.

Analysis of angiotensin II- and ACTH-driven mineralocorticoid functions and omental adiposity in a non-genetic, hyperadipose female rat phenotype

The hypothalamic damage induced by neonatal treatment with monosodium l-glutamate (MSG) induces several metabolic abnormalities, resulting in a rat hyperleptinemic-hyperadipose phenotype. This study was conducted to explore the impact of the neonatal MSG treatment, in the adult (120 days old) female rat on: (a) the in vivo and in vitro mineralocorticoid responses to ACTH and angiotensin II (AII); (b) the effect of leptin on ACTH- and AII-stimulated mineralocorticoid secretions by isolated corticoadrenal cells; and (c) abdominal adiposity characteristics. Our data indicate that, compared with age-matched controls, MSG rats displayed: (1) enhanced and reduced mineralocorticoid responses to ACTH and AII treatments, respectively, effects observed in both in vivo and in vitro conditions; (2) adrenal refractoriness to the inhibitory effect of exogenous leptin on ACTH-stimulated aldosterone output by isolated adrenocortical cells; and (3) distorted omental adiposity morphology and function. This study supports that the adult hyperleptinemic MSG female rat is characterized by enhanced ACTH-driven mineralocorticoid function, impaired adrenal leptin sensitivity, and disrupted abdominal adiposity function. MSG rats could counteract undesirable effects of glucocorticoid excess, by developing a reduced AII-driven mineralocorticoid function. Thus, chronic hyperleptinemia could play a protective role against ACTH-mediated allostatic loads in the adrenal leptin resistant, MSG female rat phenotype.

Viral transport of DNA damage that mimics a stalled replication fork.

Adeno-associated virus type 2 (AAV2) infection incites cells to arrest with 4N DNA content or die if the p53 pathway is defective. This arrest depends on AAV2 DNA, which is single stranded with inverted terminal repeats that serve as primers during viral DNA replication. Here, we show that AAV2 DNA triggers damage signaling that resembles the response to an aberrant cellular DNA replication fork. UV treatment of AAV2 enhances the G2 arrest by generating intrastrand DNA cross-links which persist in infected cells, disrupting viral DNA replication and maintaining the viral DNA in the single-stranded form. In cells, such DNA accumulates into nuclear foci with a signaling apparatus that involves DNA polymerase delta, ATR, TopBP1, RPA, and the Rad9/Rad1/Hus1 complex but not ATM or NBS1. Focus formation and damage signaling strictly depend on ATR and Chk1 functions. Activation of the Chk1 effector kinase leads to the virus-induced G2 arrest. AAV2 provides a novel way to study the cellular response to abnormal DNA replication without damaging cellular DNA. By using the AAV2 system, we show that in human cells activation of phosphorylation of Chk1 depends on TopBP1 and that it is a prerequisite for the appearance of DNA damage foci.

Integration of Bridge Damage Detection Concepts and Components (3 volumes), TR-636, 2013

This work is divided into three volumes: Volume I: Strain-Based Damage Detection; Volume II: Acceleration-Based Damage Detection; Volume III: Wireless Bridge Monitoring Hardware. Volume I: In this work, a previously-developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The statistical damage-detection tool, control-chart-based damage-detection methodologies, were further investigated and advanced. For the validation of the damage-detection approaches, strain data were obtained from a sacrificial specimen attached to the previously-utilized US 30 Bridge over the South Skunk River (in Ames, Iowa), which had simulated damage,. To provide for an enhanced ability to detect changes in the behavior of the structural system, various control chart rules were evaluated. False indications and true indications were studied to compare the damage detection ability in regard to each methodology and each control chart rule. An autonomous software program called Bridge Engineering Center Assessment Software (BECAS) was developed to control all aspects of the damage detection processes. BECAS requires no user intervention after initial configuration and training. Volume II: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The objective of this part of the project was to validate/integrate a vibration-based damage-detection algorithm with the strain-based methodology formulated by the Iowa State University Bridge Engineering Center. This report volume (Volume II) presents the use of vibration-based damage-detection approaches as local methods to quantify damage at critical areas in structures. Acceleration data were collected and analyzed to evaluate the relationships between sensors and with changes in environmental conditions. A sacrificial specimen was investigated to verify the damage-detection capabilities and this volume presents a transmissibility concept and damage-detection algorithm that show potential to sense local changes in the dynamic stiffness between points across a joint of a real structure. The validation and integration of the vibration-based and strain-based damage-detection methodologies will add significant value to Iowa’s current and future bridge maintenance, planning, and management Volume III: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. This report volume (Volume III) summarizes the energy harvesting techniques and prototype development for a bridge monitoring system that uses wireless sensors. The wireless sensor nodes are used to collect strain measurements at critical locations on a bridge. The bridge monitoring hardware system consists of a base station and multiple self-powered wireless sensor nodes. The base station is responsible for the synchronization of data sampling on all nodes and data aggregation. Each wireless sensor node include a sensing element, a processing and wireless communication module, and an energy harvesting module. The hardware prototype for a wireless bridge monitoring system was developed and tested on the US 30 Bridge over the South Skunk River in Ames, Iowa. The functions and performance of the developed system, including strain data, energy harvesting capacity, and wireless transmission quality, were studied and are covered in this volume.

Protein interaction studies point to new functions for Escherichia coli glyceraldehyde-3-phosphate dehydrogenase

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a multifunctional protein with defined functions in numerous mammalian cellular processes. GAPDH functional diversity depends on various factors such as covalent modifications, subcellular localization, oligomeric state and intracellular concentration of substrates or ligands, as well as protein-protein interactions. In bacteria, alternative GAPDH functions have been associated with its extracellular location in pathogens or probiotics. In this study, new intracellular functions of E. coli GAPDH were investigated following a proteomic approach aimed at identifying interacting partners using in vivo formaldehyde cross-linking followed by mass spectrometry. The identified proteins were involved in metabolic processes, protein synthesis and folding or DNA repair. Some interacting proteins were also identified in immunopurification experiments in the absence of cross-linking. Pull-down experiments and overlay immunoblotting were performed to further characterize the interaction with phosphoglycolate phosphatase (Gph). This enzyme is involved in the metabolism of 2-phosphoglycolate formed in the DNA repair of 3"-phosphoglycolate ends generated by bleomycin damage. We show that interaction between Gph and GAPDH increases in cells challenged with bleomycin, suggesting involvement of GAPDH in cellular processes linked to DNA repair mechanisms.