Cu(GlyGlyHis) effects on MCF7 cells: Copper uptake, reactive oxygen species generation and membrane topography changes

Elevated levels of copper have been detected in various types of human cancer cells, such as breast cancer cells, and a number of mechanisms have been proposed to explain the action and influence of copper on tumor progress. In this work, we found that stimulating the proliferation of mammary epithelial MCF7 cells with the high-redox-potential copper complex Cu (GlyGlyHis) is associated with the copper-induced intracellular generation of reactive oxygen species (ROS) that induces lipid peroxidation and causes increased roughness of external cell membranes, which leads to the formation of larger cell domes. The results presented herein provide new insights into the molecular link between copper and the proliferation of breast cancer cells and, consequently, into the mechanism by which changes in redox balance and ROS accumulation regulates cell membrane roughness. (C) 2012 Elsevier Inc. All rights reserved.

Random regression analyses using B-spline functions to model growth of Nellore cattle

The objective of this study was to estimate (co)variance components using random regression on B-spline functions to weight records obtained from birth to adulthood. A total of 82 064 weight records of 8145 females obtained from the data bank of the Nellore Breeding Program (PMGRN/Nellore Brazil) which started in 1987, were used. The models included direct additive and maternal genetic effects and animal and maternal permanent environmental effects as random. Contemporary group and dam age at calving (linear and quadratic effect) were included as fixed effects, and orthogonal Legendre polynomials of age (cubic regression) were considered as random covariate. The random effects were modeled using B-spline functions considering linear, quadratic and cubic polynomials for each individual segment. Residual variances were grouped in five age classes. Direct additive genetic and animal permanent environmental effects were modeled using up to seven knots (six segments). A single segment with two knots at the end points of the curve was used for the estimation of maternal genetic and maternal permanent environmental effects. A total of 15 models were studied, with the number of parameters ranging from 17 to 81. The models that used B-splines were compared with multi-trait analyses with nine weight traits and to a random regression model that used orthogonal Legendre polynomials. A model fitting quadratic B-splines, with four knots or three segments for direct additive genetic effect and animal permanent environmental effect and two knots for maternal additive genetic effect and maternal permanent environmental effect, was the most appropriate and parsimonious model to describe the covariance structure of the data. Selection for higher weight, such as at young ages, should be performed taking into account an increase in mature cow weight. Particularly, this is important in most of Nellore beef cattle production systems, where the cow herd is maintained on range conditions. There is limited modification of the growth curve of Nellore cattle with respect to the aim of selecting them for rapid growth at young ages while maintaining constant adult weight.

Decreasing the number of false positives in sequence classification

Abstract Background A large number of probabilistic models used in sequence analysis assign non-zero probability values to most input sequences. To decide when a given probability is sufficient the most common way is bayesian binary classification, where the probability of the model characterizing the sequence family of interest is compared to that of an alternative probability model. We can use as alternative model a null model. This is the scoring technique used by sequence analysis tools such as HMMER, SAM and INFERNAL. The most prevalent null models are position-independent residue distributions that include: the uniform distribution, genomic distribution, family-specific distribution and the target sequence distribution. This paper presents a study to evaluate the impact of the choice of a null model in the final result of classifications. In particular, we are interested in minimizing the number of false predictions in a classification. This is a crucial issue to reduce costs of biological validation. Results For all the tests, the target null model presented the lowest number of false positives, when using random sequences as a test. The study was performed in DNA sequences using GC content as the measure of content bias, but the results should be valid also for protein sequences. To broaden the application of the results, the study was performed using randomly generated sequences. Previous studies were performed on aminoacid sequences, using only one probabilistic model (HMM) and on a specific benchmark, and lack more general conclusions about the performance of null models. Finally, a benchmark test with P. falciparum confirmed these results. Conclusions Of the evaluated models the best suited for classification are the uniform model and the target model. However, the use of the uniform model presents a GC bias that can cause more false positives for candidate sequences with extreme compositional bias, a characteristic not described in previous studies. In these cases the target model is more dependable for biological validation due to its higher specificity.

Spectroscopic investigation and heat generation of Yb3+/Ho3+ codoped aluminosilicate glasses looking for the emission at 2 μm

Energy transfer (ET) and heat generation processes in Yb3+/Ho3+-codoped low-silica calcium aluminosilicate glasses were investigated using thermal lens (TL) and photoluminescence measurements looking for the emission around 2.0 μm. Stepwise ET processes from Yb3+ to Ho3+, upon excitation at 0.976 μm, produced highly efficient emission in the mid-infrared range at around 2.0 μm, with high fluorescence quantum efficiency (η1 ∼ 0.85 and independent of Ho3+ concentration) and relatively very low thermal loading (<0.4) for concentration up to 1.5% of Ho2O3. An equation was deduced for the description of the TL results that provided the absolute value of η1 and the number of emitted photons at 2.0 μm per absorbed pump photon by the Yb3+ ions, the latter reaching 60% for the highest Ho3+ concentration. These results suggest that the studied codoped system would be a promising candidate for the construction of photonic devices, especially for medical applications.

Generating multiple random exams using mathematica package and LATEX

[EN]In the framework of the European Higher Education Area, the assessment has been one of the most important aspects considered. In the Spanish Universities, one of the main differences with regard to the previous system is the incorporation of the continuous assessment to the evaluation process that is understood in several ways depending on the Universities, the courses and the lecturers. Focus on our context, a course of Mathematics of the first academic year in the Faculty of Business Administration at the University of Las Palmas de Gran Canaria (Spain), the continuous assessment has brought the preparation of a large amount of different tests to evaluate the students enrolled in it, therefore the incorporation of new tools and skills in order to make the teaching–learning process easier and more dynamic has become a need mainly in those degrees with a large number of students as the case we consider here. In this work we provide an efficient and effective way to elaborate random multiple-choice examina tion tests (although essay exams are also possible) by using Mathematica package and LATEXin order to make easier to the lectures the preparation of a large number of mid-term tests for a large number of students.

Proton magnetic resonance with parahydrogen induced polarization : Imaging strategies and continuous generation

A major challenge in imaging is the detection of small amounts of molecules of interest. In the case of magnetic resonance imaging (MRI) their signals are typically concealed by the large background signal of e.g. the tissue of the body. This problem can be tackled by hyperpolarization which increases the NMR signals up to several orders of magnitude. However, this strategy is limited for 1H, the most widely used nucleus in NMR andrnMRI, because the enormous number of protons in the body screen the small amount of hyperpolarized ones.Here, I describe a method giving rise to high 1H MRI contrast for hyperpolarized molecules against a large background signal. The contrast is based on the J-coupling induced rephasing of the NMR signal of molecules hyperpolarized via parahydrogen induce polarization (PHIP) and it can easily be implemented in common pulse sequences.rnrnHyperpolarization methods typically require expensive technical equipment (e.g. lasers or microwaves) and most techniques work only in batch mode, thus the limited lifetime of the hyperpolarization is limiting its applications. Therefore, the second part of my thesis deals with the simple and efficient generation of an hyperpolarization.These two achievements open up alternative opportunities to use the standard MRI nucleus 1H for e.g. metabolic imaging in the future.

Generation and characterization of stable, highly concentrated titanium dioxide nanoparticle aerosols for rodent inhalation studies

The intensive use of nano-sized titanium dioxide (TiO2) particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of TiO2 nanoparticles (NP) with biological systems ideally needs to be investigated using physico-chemically uniform and well-characterized NP. In this article, we describe the reproducible production of TiO2 NP aerosols using spark ignition technology. Because currently no data are available on inhaled NP in the 10–50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation studies in rodents. For anticipated in vivo dosimetry analyses, TiO2 NP were radiolabeled with 48V by proton irradiation of the titanium electrodes of the spark generator. The dissolution rate of the 48V label was about 1% within the first day. The highly concentrated, polydisperse TiO2 NP aerosol (3–6 × 106 cm−3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation, and number concentration. Extensive characterization of NP chemical composition, physical structure, morphology, and specific surface area was performed. The originally generated amorphous TiO2 NP were converted into crystalline anatase TiO2 NP by thermal annealing at 950 °C. Both crystalline and amorphous 20-nm TiO2 NP were chain agglomerated/aggregated, consisting of primary particles in the range of 5 nm. Disintegration of the deposited TiO2 NP in lung tissue was not detectable within 24 h.

Lucky numbers: Choice strategies in the Pennsylvania Daily Number game

Examined the amount of money bet during a week of Pennsylvania's Daily Number game. In this game, players receive a predetermined payoff for picking the 3-digit number (000 to 999) drawn on that day. The betting distribution was distinctly nonuniform. Several betting patterns were identified, such as picking triples and avoiding double 9s. In addition, 121 adults and 215 students were asked to rate selected numbers for randomness, luckiness, and perceived history of winning; to categorize numbers; and to free associate to numbers. It is proposed that people seem to choose highly patterned, available, and/or "lucky" numbers. People apparently do not bet numbers that reflect the random process of the game (do not utilize a representativeness heuristic).

Impact of random and systematic recall errors and selection bias in case--control studies on mobile phone use and brain tumors in adolescents (CEFALO study)

Whether the use of mobile phones is a risk factor for brain tumors in adolescents is currently being studied. Case--control studies investigating this possible relationship are prone to recall error and selection bias. We assessed the potential impact of random and systematic recall error and selection bias on odds ratios (ORs) by performing simulations based on real data from an ongoing case--control study of mobile phones and brain tumor risk in children and adolescents (CEFALO study). Simulations were conducted for two mobile phone exposure categories: regular and heavy use. Our choice of levels of recall error was guided by a validation study that compared objective network operator data with the self-reported amount of mobile phone use in CEFALO. In our validation study, cases overestimated their number of calls by 9% on average and controls by 34%. Cases also overestimated their duration of calls by 52% on average and controls by 163%. The participation rates in CEFALO were 83% for cases and 71% for controls. In a variety of scenarios, the combined impact of recall error and selection bias on the estimated ORs was complex. These simulations are useful for the interpretation of previous case-control studies on brain tumor and mobile phone use in adults as well as for the interpretation of future studies on adolescents.

Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

The Optimal Confidence Region for a Random Parameter

Under a two-level hierarchical model, suppose that the distribution of the random parameter is known or can be estimated well. Data are generated via a fixed, but unobservable realization of this parameter. In this paper, we derive the smallest confidence region of the random parameter under a joint Bayesian/frequentist paradigm. On average this optimal region can be much smaller than the corresponding Bayesian highest posterior density region. The new estimation procedure is appealing when one deals with data generated under a highly parallel structure, for example, data from a trial with a large number of clinical centers involved or genome-wide gene-expession data for estimating individual gene- or center-specific parameters simultaneously. The new proposal is illustrated with a typical microarray data set and its performance is examined via a small simulation study.

Energy harvesting from body motion using rotational micro-generation

Autonomous system applications are typically limited by the power supply operational lifetime when battery replacement is difficult or costly. A trade-off between battery size and battery life is usually calculated to determine the device capability and lifespan. As a result, energy harvesting research has gained importance as society searches for alternative energy sources for power generation. For instance, energy harvesting has been a proven alternative for powering solar-based calculators and self-winding wristwatches. Thus, the use of energy harvesting technology can make it possible to assist or replace batteries for portable, wearable, or surgically-implantable autonomous systems. Applications such as cardiac pacemakers or electrical stimulation applications can benefit from this approach since the number of surgeries for battery replacement can be reduced or eliminated. Research on energy scavenging from body motion has been investigated to evaluate the feasibility of powering wearable or implantable systems. Energy from walking has been previously extracted using generators placed on shoes, backpacks, and knee braces while producing power levels ranging from milliwatts to watts. The research presented in this paper examines the available power from walking and running at several body locations. The ankle, knee, hip, chest, wrist, elbow, upper arm, side of the head, and back of the head were the chosen target localizations. Joints were preferred since they experience the most drastic acceleration changes. For this, a motor-driven treadmill test was performed on 11 healthy individuals at several walking (1-4 mph) and running (2-5 mph) speeds. The treadmill test provided the acceleration magnitudes from the listed body locations. Power can be estimated from the treadmill evaluation since it is proportional to the acceleration and frequency of occurrence. Available power output from walking was determined to be greater than 1mW/cm³ for most body locations while being over 10mW/cm³ at the foot and ankle locations. Available power from running was found to be almost 10 times higher than that from walking. Most energy harvester topologies use linear generator approaches that are well suited to fixed-frequency vibrations with sub-millimeter amplitude oscillations. In contrast, body motion is characterized with a wide frequency spectrum and larger amplitudes. A generator prototype based on self-winding wristwatches is deemed to be appropriate for harvesting body motion since it is not limited to operate at fixed-frequencies or restricted displacements. Electromagnetic generation is typically favored because of its slightly higher power output per unit volume. Then, a nonharmonic oscillating rotational energy scavenger prototype is proposed to harness body motion. The electromagnetic generator follows the approach from small wind turbine designs that overcome the lack of a gearbox by using a larger number of coil and magnets arrangements. The device presented here is composed of a rotor with multiple-pole permanent magnets having an eccentric weight and a stator composed of stacked planar coils. The rotor oscillations induce a voltage on the planar coil due to the eccentric mass unbalance produced by body motion. A meso-scale prototype device was then built and evaluated for energy generation. The meso-scale casing and rotor were constructed on PMMA with the help of a CNC mill machine. Commercially available discrete magnets were encased in a 25mm rotor. Commercial copper-coated polyimide film was employed to manufacture the planar coils using MEMS fabrication processes. Jewel bearings were used to finalize the arrangement. The prototypes were also tested at the listed body locations. A meso-scale generator with a 2-layer coil was capable to extract up to 234 µW of power at the ankle while walking at 3mph with a 2cm³ prototype for a power density of 117 µW/cm³. This dissertation presents the analysis of available power from walking and running at different speeds and the development of an unobtrusive miniature energy harvesting generator for body motion. Power generation indicates the possibility of powering devices by extracting energy from body motion.

RAPID SPACE TRAJECTORY GENERATION USING A FOURIER SERIES SHAPE-BASED APPROACH

With the insatiable curiosity of human beings to explore the universe and our solar system, it is essential to benefit from larger propulsion capabilities to execute efficient transfers and carry more scientific equipment. In the field of space trajectory optimization the fundamental advances in using low-thrust propulsion and exploiting the multi-body dynamics has played pivotal role in designing efficient space mission trajectories. The former provides larger cumulative momentum change in comparison with the conventional chemical propulsion whereas the latter results in almost ballistic trajectories with negligible amount of propellant. However, the problem of space trajectory design translates into an optimal control problem which is, in general, time-consuming and very difficult to solve. Therefore, the goal of the thesis is to address the above problem by developing a methodology to simplify and facilitate the process of finding initial low-thrust trajectories in both two-body and multi-body environments. This initial solution will not only provide mission designers with a better understanding of the problem and solution but also serves as a good initial guess for high-fidelity optimal control solvers and increases their convergence rate. Almost all of the high-fidelity solvers enjoy the existence of an initial guess that already satisfies the equations of motion and some of the most important constraints. Despite the nonlinear nature of the problem, it is sought to find a robust technique for a wide range of typical low-thrust transfers with reduced computational intensity. Another important aspect of our developed methodology is the representation of low-thrust trajectories by Fourier series with which the number of design variables reduces significantly. Emphasis is given on simplifying the equations of motion to the possible extent and avoid approximating the controls. These facts contribute to speeding up the solution finding procedure. Several example applications of two and three-dimensional two-body low-thrust transfers are considered. In addition, in the multi-body dynamic, and in particular the restricted-three-body dynamic, several Earth-to-Moon low-thrust transfers are investigated.

Comparison of Newer-Generation Drug-Eluting With Bare-Metal Stents in Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pooled Analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) Trials

OBJECTIVES This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. METHODS Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. RESULTS Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Splitting of a prevalent Mycobacterium bovis spoligotype by variable-number tandem-repeat typing reveals high heterogeneity in an evolving clonal group

Mycobacterium bovis populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115 M. bovis isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by M. bovis SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.