Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses

Objective - The purpose of this study was to assess cardiac function and cell damage in intrauterine growth-restricted (IUGR) fetuses across clinical Doppler stages of deterioration. Study Design - One hundred twenty appropriate-for-gestational-age and 81 IUGR fetuses were classified in stages 1/2/3 according umbilical artery present/absent/reversed end-diastolic blood flow, respectively. Cardiac function was assessed by modified-myocardial performance index, early-to-late diastolic filling ratios, cardiac output, and cord blood B-type natriuretic peptide; myocardial cell damage was assessed by heart fatty acid–binding protein, troponin-I, and high-sensitivity C-reactive protein. Results - Modified-myocardial performance index, blood B-type natriuretic peptide, and early-to-late diastolic filling ratios were increased in a stage-dependent manner in IUGR fetuses, compared with appropriate-for-gestational-age fetuses. Heart fatty acid–binding protein levels were higher in IUGR fetuses at stage 3, compared with control fetuses. Cardiac output, troponin-I, and high-sensitivity C-reactive protein did not increase in IUGR fetuses at any stage. Conclusion - IUGR fetuses showed signs of cardiac dysfunction from early stages. Cardiac dysfunction deteriorates further with the progression of fetal compromise, together with the appearance of biochemical signs of cell damage.

Optimal Control of Heterogeneous Systems

Цветомир Цачев - В настоящия доклад се прави преглед на някои резултати от областта на оптималното управление на непрекъснатите хетерогенни системи, публикувани в периодичната научна литература в последните години. Една динамична система се нарича хетерогенна, ако всеки от нейните елементи има собствена динамиката. Тук разглеждаме оптимално управление на системи, чиято хетерогенност се описва с едномерен или двумерен параметър – на всяка стойност на параметъра отговаря съответен елемент на системата. Хетерогенните динамични системи се използват за моделиране на процеси в икономиката, епидемиологията, биологията, опазване на обществената сигурност (ограничаване на използването на наркотици) и др. Тук разглеждаме модел на оптимално инвестиране в образование на макроикономическо ниво [11], на ограничаване на последствията от разпространението на СПИН [9], на пазар на права за въглеродни емисии [3, 4] и на оптимален макроикономически растеж при повишаване на нивото на върховите технологии [1]. Ключови думи: оптимално управление, непрекъснати хетерогенни динамични системи, приложения в икономиката и епидемиолегията

The effects of defendant account on damage award decisions

The purpose of this study was to examine whether the manner in which civil defendants account for their behavior influences compensatory and punitive damage awards. Jurors read three civil trial summaries, in which I manipulated injury severity (high vs. low), defendant reprehensibility (high vs. low), defendant status (individual vs. corporate), and account (concession, excuse, justification or refusal) in a factorial design. I also included four control groups in which the defendant stipulated liability. In all other conditions, participants read that a jury had found the defendant negligent. Only defendant reprehensibility influenced punitive awards. Both plaintiff injury and defendant reprehensibility influenced compensatory awards. When individuals offered justifications and when corporations offered excuses, jurors awarded lower compensatory awards against low reprehensibility defendants than against high reprehensibility defendants. Negligence stipulations led to lower damage awards for individuals than for corporations. Additionally, concessions tended to produce lower awards when combined with a stipulation of negligence as opposed to a jury decision. These findings support the hypothesis that in cases in which the defendant is clearly negligent, circumstances exist in which stipulating negligence and offering an apologetic account will lead to reduced damage awards decisions. Results indicate that individual and corporate defendants offering justifications and refusals should first consider the reprehensibility of their actions. In a broader realm, findings demonstrate that the manner in which a jury perceives the explanation given by the defendant is dependent upon defendant characteristics and case-specific factors. ^

File Control: The Heart Of Business Computer Management

In his study - File Control: The Heart Of Business Computer Management - William G. O'Brien, Assistant Professor, The School of Hospitality Management at Florida International University, initially informs you: “Even though computers are an everyday part of the hospitality industry, many managers lack the knowledge and experience to control and protect the files in these systems. The author offers guidelines which can minimize or prevent damage to the business as a whole.” Our author initially opens this study with some anecdotal instances illustrating the failure of hospitality managers to exercise due caution with regard to computer supported information systems inside their restaurants and hotels. “Of the three components that make up any business computer system (data files, programs, and hard-ware), it is files that are most important, perhaps irreplaceable, to the business,” O’Brien informs you. O’Brien breaks down the noun, files, into two distinct categories. They are, the files of extrinsic value, and its counterpart the files of intrinsic value. An example of extrinsic value files would be a restaurant’s wine inventory. “As sales are made and new shipments are received, the computer updates the file,” says O’Brien. “This information might come directly from a point-of-sale terminal or might be entered manually by an employee,” he further explains. On the intrinsic side of the equation, O’Brien wants you to know that the information itself is the valuable part of this type of file. Its value is over and above the file’s informational purpose as a pragmatic business tool, as it is in inventory control. “The information is money in the legal sense For instance, figures moved about in banking system computers do not represent dollars; they are dollars,” O’Brien explains. “If the record of a dollar amount is erased from all computer files, then that money ceases to exist,” he warns. This type of information can also be bought and sold, such as it is in customer lists to advertisers. Files must be protected O’Brien stresses. “File security requires a systematic approach,” he discloses. O’Brien goes on to explain important elements to consider when evaluating file information. File back-up is also an important factor to think about, along with file storage/safety concerns. “Sooner or later, every property will have its fire, flood, careless mistake, or disgruntled employee,” O’Brien closes. “…good file control can minimize or prevent damage to the business as a whole.”

Detection of seismic damage in buildings using time series analysis and pattern recognition

Peer reviewed

Performance of a single liquid column damper for the control of dynamic responses of a tension leg platform

Tuned liquid column dampers have been proved to be successful in mitigating the dynamic responses of civil infrastructure. There have been some recent applications of this concept on wind turbines and this passive control system can help to mitigate responses of offshore floating platforms and wave devices. The control of dynamic responses of these devices is important for reducing loads on structural elements and facilitating operations and maintenance (O&M) activities. This paper outlines the use of a tuned single liquid column damper for the control of a tension leg platform supported wind turbine. Theoretical studies were carried out and a scaled model was tested in a wave basin to assess the performance of the damper. The tests on the model presented in this paper correspond to a platform with a very low natural frequency for surge, sway and yaw motions. For practical purposes, it was not possible to tune the liquid damper exactly to this frequency. The consequent approach taken and the efficiency of such approach are presented in this paper. Responses to waves of a single frequency are investigated along with responses obtained from wave spectra characterising typical sea states. The extent of control is quantified using peak and root mean squared dynamic responses respectively. The tests present some guidelines and challenges for testing scaled devices in relation to including response control mechanisms. Additionally, the results provide a basis for dictating future research on tuned liquid column damper based control on floating platforms.

Dual roles of DNA repair enzymes in RNA biology/post-transcriptional control

Despite consistent research into the molecular principles of the DNA damage repair pathway for almost two decades, it has only recently been found that RNA metabolism is very tightly related to this pathway, and the two ancient biochemical mechanisms act in alliance to maintain cellular genomic integrity. The close links between these pathways are well exemplified by examining the base excision repair pathway, which is now well known for dual roles of many of its members in DNA repair and RNA surveillance, including APE1, SMUG1, and PARP1. With additional links between these pathways steadily emerging, this review aims to provide a summary of the emerging roles for DNA repair proteins in the post-transcriptional regulation of RNAs. 

Restoring function after neuromuscular trauma: novel paradigms for enhancing volitional control of neural activity in untethered environments and vHAB, a gamified therapy platform

Thesis (Ph.D.)--University of Washington, 2016-08

Assessing Potential Laser Strike Protection Engineering Control for United States Coast Guard Aircraft

Thesis (Master's)--University of Washington, 2016-06

Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoring

Antineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG) enzyme, it specifically detects DNA oxidative damage. The aim of this study was to investigate genotoxic effects in workers occupationally exposed to cytostatics (n = 46), as compared to a control group with no exposure (n = 46) at two Portuguese hospitals, by means of the alkaline comet assay. The potential of the OGG1 Ser326Cys polymorphism as a susceptibility biomarker was also investigated. Exposure was evaluated by investigating the contamination of surfaces and genotoxic assessment was done by alkaline comet assay in peripheral blood lymphocytes. OGG1 Ser326Cys (rs1052133) polymorphism was studied by Real Time PCR. As for exposure assessment, there were 121 (37%) positive samples out of a total of 327 samples analysed from both hospitals. No statistically significant differences (Mann-Whitney test, p > 0.05) were found between subjects with and without exposure, regarding DNA damage and oxidative DNA damage, nevertheless the exposed group exhibited higher values. Moreover, there was no consistent trend regarding the variation of both biomarkers as assessed by comet assay with OGG1 polymorphism. Our study was not statistically significant regarding occupational exposure to antineoplastic drugs and genetic damage assessed by comet assay. However, health professionals should be monitored for risk behaviour, in order to ensure that safety measures are applied and protection devices are used correctly.

CHARACTERIZATION OF RADIATION DAMAGE TO A NOVEL PHOTONIC CRYSTAL SENSOR

New methods of nuclear fuel and cladding characterization must be developed and implemented to enhance the safety and reliability of nuclear power plants. One class of such advanced methods is aimed at the characterization of fuel performance by performing minimally intrusive in-core, real time measurements on nuclear fuel on the nanometer scale. Nuclear power plants depend on instrumentation and control systems for monitoring, control and protection. Traditionally, methods for fuel characterization under irradiation are performed using a “cook and look” method. These methods are very expensive and labor-intensive since they require removal, inspection and return of irradiated samples for each measurement. Such fuel cladding inspection methods investigate oxide layer thickness, wear, dimensional changes, ovality, nuclear fuel growth and nuclear fuel defect identification. These methods are also not suitable for all commercial nuclear power applications as they are not always available to the operator when needed. Additionally, such techniques often provide limited data and may exacerbate the phenomena being investigated. This thesis investigates a novel, nanostructured sensor based on a photonic crystal design that is implemented in a nuclear reactor environment. The aim of this work is to produce an in-situ radiation-tolerant sensor capable of measuring the deformation of a nuclear material during nuclear reactor operations. The sensor was fabricated on the surface of nuclear reactor materials (specifically, steel and zirconium based alloys). Charged-particle and mixed-field irradiations were both performed on a newly-developed “pelletron” beamline at Idaho State University's Research and Innovation in Science and Engineering (RISE) complex and at the University of Maryland's 250 kW Training Reactor (MUTR). The sensors were irradiated to 6 different fluences (ranging from 1 to 100 dpa), followed by intensive characterization using focused ion beam (FIB), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to investigate the physical deformation and microstructural changes between different fluence levels, to provide high-resolution information regarding the material performance. Computer modeling (SRIM/TRIM) was employed to simulate damage to the sensor as well as to provide significant information concerning the penetration depth of the ions into the material.

The role of intracellular calcium perturbations in muscle damage and dysfunction in mouse models of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. DMD is clinically characterized by severe, progressive and irreversible loss of muscle function, in which most patients lose the ability to walk by their early teens and die by their early 20’s. Impaired intracellular calcium (Ca2+) regulation and activation of cell degradation pathways have been proposed as key contributors to DMD disease progression. This dissertation research consists of three studies investigating the role of intracellular Ca2+ in skeletal muscle dysfunction in different mouse models of DMD. Study one evaluated the role of Ca2+-activated enzymes (proteases) that activate protein degradation in excitation-contraction (E-C) coupling failure following repeated contractions in mdx and dystrophin-utrophin null (mdx/utr-/-) mice. Single muscle fibers from mdx/utr-/- mice had greater E-C coupling failure following repeated contractions compared to fibers from mdx mice. Moreover, protease inhibition during these contractions was sufficient to attenuate E-C coupling failure in muscle fibers from both mdx and mdx/utr-/- mice. Study two evaluated the effects of overexpressing the Ca2+ buffering protein sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 (SERCA1) in skeletal muscles from mdx and mdx/utr-/- mice. Overall, SERCA1 overexpression decreased muscle damage and protected the muscle from contraction-induced injury in mdx and mdx/utr-/- mice. In study three, the cellular mechanisms underlying the beneficial effects of SERCA1 overexpression in mdx and mdx/utr-/- mice were investigated. SERCA1 overexpression attenuated calpain activation in mdx muscle only, while partially attenuating the degradation of the calpain target desmin in mdx/utr-/- mice. Additionally, SERCA1 overexpression decreased the SERCA-inhibitory protein sarcolipin in mdx muscle but did not alter levels of Ca2+ regulatory proteins (parvalbumin and calsequestrin) in either dystrophic model. Lastly, SERCA1 overexpression blunted the increase in endoplasmic reticulum stress markers Grp78/BiP in mdx mice and C/EBP homologous protein (CHOP) in mdx and mdx/utr-/- mice. Overall, findings from the studies presented in this dissertation provide new insight into the role of Ca2+ in muscle dysfunction and damage in different dystrophic mouse models. Further, these findings support the overall strategy for improving intracellular Ca2+ control for the development of novel therapies for DMD.

Self-sealing of thermal fatigue and mechanical damage in fiber-reinforced composite materials

Fiber reinforced composite tanks provide a promising method of storage for liquid oxygen and hydrogen for aerospace applications. The inherent thermal fatigue of these vessels leads to the formation of microcracks, which allow gas phase leakage across the tank walls. In this dissertation, self-healing functionality is imparted to a structural composite to effectively seal microcracks induced by both mechanical and thermal loading cycles. Two different microencapsulated healing chemistries are investigated in woven glass fiber/epoxy and uni-weave carbon fiber/epoxy composites. Self-healing of mechanically induced damage was first studied in a room temperature cured plain weave E-glass/epoxy composite with encapsulated dicyclopentadiene (DCPD) monomer and wax protected Grubbs' catalyst healing components. A controlled amount of microcracking was introduced through cyclic indentation of opposing surfaces of the composite. The resulting damage zone was proportional to the indentation load. Healing was assessed through the use of a pressure cell apparatus to detect nitrogen flow through the thickness direction of the damaged composite. Successful healing resulted in a perfect seal, with no measurable gas flow. The effect of DCPD microcapsule size (51 um and 18 um) and concentration (0 - 12.2 wt%) on the self-sealing ability was investigated. Composite specimens with 6.5 wt% 51 um capsules sealed 67% of the time, compared to 13% for the control panels without healing components. A thermally stable, dual microcapsule healing chemistry comprised of silanol terminated poly(dimethyl siloxane) plus a crosslinking agent and a tin catalyst was employed to allow higher composite processing temperatures. The microcapsules were incorporated into a satin weave E-glass fiber/epoxy composite processed at 120C to yield a glass transition temperature of 127C. Self-sealing ability after mechanical damage was assessed for different microcapsule sizes (25 um and 42 um) and concentrations (0 - 11 vol%). Incorporating 9 vol% 42 um capsules or 11 vol% 25 um capsules into the composite matrix leads to 100% of the samples sealing. The effect of microcapsule concentration on the short beam strength, storage modulus, and glass transition temperature of the composite specimens was also investigated. The thermally stable tin catalyzed poly(dimethyl siloxane) healing chemistry was then integrated into a [0/90]s uniweave carbon fiber/epoxy composite. Thermal cycling (-196C to 35C) of these specimens lead to the formation of microcracks, over time, formed a percolating crack network from one side of the composite to the other, resulting in a gas permeable specimen. Crack damage accumulation and sample permeability was monitored with number of cycles for both self-healing and traditional non-healing composites. Crack accumulation occurred at a similar rate for all sample types tested. A 63% increase in lifetime extension was achieved for the self-healing specimens over traditional non-healing composites.

Spectral damage model for lighted museum paintings: Oil, acrylic and gouache

A spectral aging test was developed to estimate the photochemical damage of oil, acrylic and gouache paints exposed to permanent lighting. The paints were irradiated at seven different wavelengths in the optical range to control and evaluate their spectral behaviour. To reach this objective, boxes with isolated aging cells were made. In each of box, one LED of a different wavelength and one photodiode were installed. Inside the boxes, the temperature of an exhibit area was recreated through a thermocouple sensor that controlled the temperature using a fan. The heat produced by the LED was dissipated by a thermal radiator. Moreover, to evaluate the exposure time dependence of the irradiation level, the test was performed using two different irradiation levels in ten exposure series. After each series, the spectral reflectance was measured, and the data collected for each paint and wavelength were used to develop a model of damage produced by the interaction between the spectral radiant exposure and the paint.

Leccinum vulpinum Watling induces DNA damage, decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line

The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control. Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity.