Cediranib: a VEGF receptor tyrosine kinase inhibitor

Cediranib is a potent inhibitor of the VEGF family receptor tyrosine kinases, and a new agent in cancer treatment. The drug has shown promising activity in a variety of solid malignancies, in preclinical models and in clinical trials. Its pharmacokinetics allow for a convenient once-daily administration, with a toxicity profile that is very similar to other VEGF inhibitors. Its main side effects include hypertension, nausea, dysphonia, fatigue and diarrhea. Adverse events seem to be manageable, especially when used in doses lower than 45 mg/day. Studies have shown some activity as a single agent or in combination in advanced tumors, but not enough to secure its approval for routine use up to now. Clinical trials are still evaluating the role of cediranib in combination chemotherapy with cytotoxic agents.

RHEOLOGICAL EVALUATION OF THE STRUCTURE OF ICE CREAM MIXES VARYING FAT BASE

This paper discusses the influence of fat type in the structure of ice cream, during its production by means of rheo-optical analysis. Fat plays an important part in the ice cream structure formation. It's responsible for the air stabilization, flavor release, texture and melting properties. The objective of this study was to use a rheological method to predict the fat network formation in ice cream with three types of fats (hydrogenated, low trans and palm fat). The three formulations were produced using the same methodology and ratio of ingredients. Rheo-optical measurements were taken before and after the ageing process, and the maximum compression force, overrun and melting profile were calculated in the finished product. The rheological analysis showed a better response from the ageing process from the hydrogenated fat, followed by the low trans fat. The formulation with palm fat showed greater differences between the three, where through the rheological tests a weaker destabilization of the fat globule membrane by the emulsifier was suggested. The overrun, texture measurements and meltdown profile has shown the distinction on the structure formation by the hydrogenated fat from the other fats.

Electromagnetic torque ripple and copper losses reduction in permanent magnet synchronous machines

This paper presents a method for electromagnetic torque ripple and copper losses reduction in (non-sinusoidal or trapezoidal) surface-mount permanent magnet synchronous machines (SM-PMSM). The method is based on an extension of classical dq transformation that makes it possible to write a vectorial model for this kind of machine (with a non-sinusoidal back-EMF waveform). This model is obtained by the application of that transformation in the classical machine per-phase model. That transformation can be applied to machines that have any type of back-EMF waveform, and not only trapezoidal or square-wave back-EMF waveforms. Implementation results are shown for an electrical converter, using the proposed vectorial model, feeding a non-sinusoidal synchronous machine (brushless DC motor). They show that the use of this vectorial mode is a way to achieve improvements in the performance of this kind of machine, considering the electromagnetic torque ripple and copper losses, if compared to a drive system that employs a classical six-step mode as a converter. Copyright (C) 2011 John Wiley & Sons, Ltd.

Self-reported hearing loss among elderly individuals in the city of Sao Paulo, Brazil: prevalence and associated factors (SABE Study, 2006)

This article describes the prevalence of self-reported hearing loss in an elderly population in the city of Sao Paulo, Brazil, and associated factors, based on a cross-sectional descriptive and quantitative study. The sample consisted of individuals over 65 years of age selected from census tracts in two stages, with replacement and probability proportional to the population 75 years of age or older. Statistical analysis used Stata 10 with weighted data, Rao-Scott test, and backward stepwise Poisson regression. 1,115 elders were interviewed. Prevalence of self-reported hearing loss was 30.4%, and higher levels were associated with age over 75 years, male gender, self-reported musculoskeletal conditions, dizziness, visual impairment, and difficulty using the telephone. Increased knowledge of factors associated with hearing loss would support public policies on hearing. The high prevalence found in this study underlines the importance of addressing this issue among the elderly.

TEMPERTURE INFLUENCE ON THE RHEOLOGICAL BEHAVIOUR OF CEMENTITOUS PASTES PREPARED WITH AIR-ENTRAINING ADMIXTURES

Cementitious pastes prepared with air-entraining admixtures (AEA) are very sensitive to mix procedures and environmental conditions. Some of the effects of AEA on the properties of cementitious material are discussed in literature, although for the most part, only in the hardened state. However, the impact temperature has on air-incorporation during the early age stages and on consolidation has been little investigated and as such, is the objective of this work. Thus, pastes formulated with Portland cement and air-entraining admixtures are evaluated in this work with a focus on the role temperature plays in the early age behavior. The results show that air-incorporation was affected by environmental conditions which caused changes in the kinematic viscosity and rate of consolidation.

Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome

Objective To evaluate the changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization in the ICU and their relation to outcome. Design Prospective observational study. Setting ICU of a veterinary university medical center. Animals Thirty dogs with severe sepsis or septic shock caused by pyometra who underwent surgery and were admitted to the ICU. Measurements and Main Results Severe sepsis was defined as the presence of sepsis and sepsis-induced dysfunction of one or more organs. Septic shock was defined as the presence of severe sepsis plus hypotension not reversed with fluid resuscitation. After the presumptive diagnosis of sepsis secondary to pyometra, blood samples were collected and clinical findings were recorded. Volume resuscitation with 0.9% saline solution and antimicrobial therapy were initiated. Following abdominal ultrasonography and confirmation of increased uterine volume, dogs underwent corrective surgery. After surgery, the animals were admitted to the ICU, where resuscitation was guided by the clinical parameters, central venous oxygen saturation (ScvO2), lactate, and base deficit. Between survivors and nonsurvivors it was observed that the ScvO2, lactate, and base deficit on ICU admission were each related independently to death (P = 0.001, P = 0.030, and P < 0.001, respectively). ScvO2 and base deficit were found to be the best discriminators between survivors and nonsurvivors as assessed via receiver operator characteristic curve analysis. Conclusion Our study suggests that ScvO2 and base deficit are useful in predicting the prognosis of dogs with severe sepsis and septic shock; animals with a higher ScvO2 and lower base deficit at admission to the ICU have a lower probability of death.

Effects of Natural Radiation, Photosynthetically Active Radiation and Artificial Ultraviolet Radiation-B on the Chloroplast Organization and Metabolism of Porphyra acanthophora var. brasiliensis (Rhodophyta, Bangiales)

We undertook a study of Porphyra acanthophora var. brasiliensis to determine its responses under ambient conditions, photosynthetically active radiation (PAR), and PAR+UVBR (ultraviolet radiation-B) treatment, focusing on changes in ultrastructure, and cytochemistry. Accordingly, control ambient samples were collected in the field, and two different treatments were performed in the laboratory. Plants were exposed to PAR at 60 mu mol photons m(-2) s(-1) and PAR+UVBR at 0.35 W m(-2) for 3 h per day during 21 days of in vitro cultivation. Confocal laser scanning microscopy analysis of the vegetative cells showed single stellate chloroplast in ambient and PAR samples, but in PAR+UVBR-exposed plants, the chloroplast showed alterations in the number and form of arms. Under PAR+UVBR treatment, the thylakoids of the chloroplasts were disrupted, and an increase in the number of plastoglobuli was observed, in addition to mitochondria, which appeared with irregular, disrupted morphology compared to ambient and PAR samples. After UVBR exposure, the formation of carpospores was also observed. Plants under ambient conditions, as well as those treated with PAR and PAR+UVBR, all showed different concentrations of enzymatic response, including glutathione peroxidase and reductase activity. In summary, the present study demonstrates that P. acanthophora var. brasiliensis shows the activation of distinct mechanisms against natural radiation, PAR and PAR+UVBR.

Constraining anomalous Higgs boson interactions

The recently announced Higgs boson discovery marks the dawn of the direct probing of the electroweak symmetry breaking sector. Sorting out the dynamics responsible for electroweak symmetry breaking now requires probing the Higgs boson interactions and searching for additional states connected to this sector. In this work, we analyze the constraints on Higgs boson couplings to the standard model gauge bosons using the available data from Tevatron and LHC. We work in a model-independent framework expressing the departure of the Higgs boson couplings to gauge bosons by dimension-six operators. This allows for independent modifications of its couplings to gluons, photons, and weak gauge bosons while still preserving the Standard Model (SM) gauge invariance. Our results indicate that best overall agreement with data is obtained if the cross section of Higgs boson production via gluon fusion is suppressed with respect to its SM value and the Higgs boson branching ratio into two photons is enhanced, while keeping the production and decays associated to couplings to weak gauge bosons close to their SM prediction.

Canonical Quantization of a Massive Weyl Field

We construct a consistent theory of a quantum massive Weyl field. We start with the formulation of the classical field theory approach for the description of massive Weyl fields. It is demonstrated that the standard Lagrange formalism cannot be applied for the studies of massive first-quantized Weyl spinors. Nevertheless we show that the classical field theory description of massive Weyl fields can be implemented in frames of the Hamilton formalism or using the extended Lagrange formalism. Then we carry out a canonical quantization of the system. The independent ways for the quantization of a massive Weyl field are discussed. We also compare our results with the previous approaches for the treatment of massive Weyl spinors. Finally the new interpretation of the Majorana condition is proposed.

LARGE-SCALE DISTRIBUTION OF ARRIVAL DIRECTIONS OF COSMIC RAYS DETECTED ABOVE 10(18) eV AT THE PIERRE AUGER OBSERVATORY

A thorough search for large-scale anisotropies in the distribution of arrival directions of cosmic rays detected above 10(18) eV at the Pierre Auger Observatory is presented. This search is performed as a function of both declination and right ascension in several energy ranges above 10(18) eV, and reported in terms of dipolar and quadrupolar coefficients. Within the systematic uncertainties, no significant deviation from isotropy is revealed. Assuming that any cosmic-ray anisotropy is dominated by dipole and quadrupole moments in this energy range, upper limits on their amplitudes are derived. These upper limits allow us to test the origin of cosmic rays above 10(18) eV from stationary Galactic sources densely distributed in the Galactic disk and predominantly emitting light particles in all directions.

Conformation analysis of a surface loop that controls active site access in the GH11 xylanase A from Bacillus subtilis

Xylanases (EC 3.2.1.8 endo-1,4-glycosyl hydrolase) catalyze the hydrolysis of xylan, an abundant hemicellulose of plant cell walls. Access to the catalytic site of GH11 xylanases is regulated by movement of a short beta-hairpin, the so-called thumb region, which can adopt open or closed conformations. A crystallographic study has shown that the D11F/R122D mutant of the GH11 xylanase A from Bacillus subtilis (BsXA) displays a stable "open" conformation, and here we report a molecular dynamics simulation study comparing this mutant with the native enzyme over a range of temperatures. The mutant open conformation was stable at 300 and 328 K, however it showed a transition to the closed state at 338 K. Analysis of dihedral angles identified thumb region residues Y113 and T123 as key hinge points which determine the open-closed transition at 338 K. Although the D11F/R122D mutations result in a reduction in local inter-intramolecular hydrogen bonding, the global energies of the open and closed conformations in the native enzyme are equivalent, suggesting that the two conformations are equally accessible. These results indicate that the thumb region shows a broader degree of energetically permissible conformations which regulate the access to the active site region. The R122D mutation contributes to the stability of the open conformation, but is not essential for thumb dynamics, i.e., the wild type enzyme can also adapt to the open conformation.

Experimental diabetes modulates collagen remodelling of joints in rats

The aim of this study was to evaluate extracellular matrix components in articular cartilage, ligaments and synovia in an experimental model of diabetes. Young Wistar rats were divided into a streptozotocin-induced (STZ; 35 mg/kg) diabetic group (DG; n=15) and a control group (CG; n=15). Weight, blood glucose and plasma anti-carboxymethyllysine were measured 70 days after STZ infusions. Knee joints, patellar ligaments, and lateral and medial collateral ligaments were isolated and stained with hematoxylineosin and Picrosirius. The total collagen content was determined by morphometry. Immunofluorescence was employed to evaluate types I, III, and V collagen in ligaments and synovial tissues and types II and XI collagen in cartilage. Results: Higher blood glucose levels and plasma anti-carboxymethyllysine were observed in DG rats when compared to those in CG rats. The final weight was significantly lower in the DG rats than in the CG rats. Histomorphometric evaluation depicted a small quantity of collagen fibers in ligaments and articular cartilage in DG rats, as well as increased collagen in synovial tissue. There was a decrease in cartilage proteoglycans in DG rats when compared with CG rats. Immunofluorescence staining revealed an increase of collagen III and V in ligaments, collagen XI in cartilage, and collagen I in synovial tissue of DG rats compared with CG rats. Conclusion: The ligaments, cartilage and synovia are highly affected following STZ-induced diabetes in rats, due the remodeling of collagen types in these tissues. This process may promote the degradation of the extracellular matrix, thus compromising joint function. Our data may help to better understand the pathogenesis of joint involvement related to diabetes.

CD44(+)/CD24(-) cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), antihuman CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumorinitiating cells in stage I and II breast cancer.

Energy-level statistics of interacting trapped bosons

It is a well-established fact that statistical properties of energy-level spectra are the most efficient tool to characterize nonintegrable quantum systems. The statistical behavior of different systems such as complex atoms, atomic nuclei, two-dimensional Hamiltonians, quantum billiards, and noninteracting many bosons has been studied. The study of statistical properties and spectral fluctuations in interacting many-boson systems has developed interest in this direction. We are especially interested in weakly interacting trapped bosons in the context of Bose-Einstein condensation (BEC) as the energy spectrum shows a transition from a collective nature to a single-particle nature with an increase in the number of levels. However this has received less attention as it is believed that the system may exhibit Poisson-like fluctuations due to the existence of an external harmonic trap. Here we compute numerically the energy levels of the zero-temperature many-boson systems which are weakly interacting through the van der Waals potential and are confined in the three-dimensional harmonic potential. We study the nearest-neighbor spacing distribution and the spectral rigidity by unfolding the spectrum. It is found that an increase in the number of energy levels for repulsive BEC induces a transition from a Wigner-like form displaying level repulsion to the Poisson distribution for P(s). It does not follow the Gaussian orthogonal ensemble prediction. For repulsive interaction, the lower levels are correlated and manifest level-repulsion. For intermediate levels P(s) shows mixed statistics, which clearly signifies the existence of two energy scales: external trap and interatomic interaction, whereas for very high levels the trapping potential dominates, generating a Poisson distribution. Comparison with mean-field results for lower levels are also presented. For attractive BEC near the critical point we observe the Shnirelman-like peak near s = 0, which signifies the presence of a large number of quasidegenerate states.