Characterization of gait in female patients with moderate to severe hallux valgus deformity.

BACKGROUND: Hallux valgus is one of the most common forefoot problems in females. Studies have looked at gait alterations due to hallux valgus deformity, assessing temporal, kinematic or plantar pressure parameters individually. The present study, however, aims to assess all listed parameters at once and to isolate the most clinically relevant gait parameters for moderate to severe hallux valgus deformity with the intent of improving post-operative patient prognosis and rehabilitation. METHODS: The study included 26 feet with moderate to severe hallux valgus deformity and 30 feet with no sign of hallux valgus in female participants. Initially, weight bearing radiographs and foot and ankle clinical scores were assessed. Gait assessment was then performed utilizing pressure insoles (PEDAR®) and inertial sensors (Physilog®) and the two groups were compared using a non-parametric statistical hypothesis test (Wilcoxon rank sum, P<0.05). Furthermore, forward stepwise regression was used to reduce the number of gait parameters to the most clinically relevant and correlation of these parameters was assessed with the clinical score. FINDINGS: Overall, the results showed clear deterioration in several gait parameters in the hallux valgus group compared to controls and 9 gait parameters (effect size between 1.03 and 1.76) were successfully isolated to best describe the altered gait in hallux valgus deformity (r(2)=0.71) as well as showed good correlation with clinical scores. INTERPRETATION: Our results, and nine listed parameters, could serve as benchmark for characterization of hallux valgus and objective evaluation of treatment efficacy.

Comparison between Radiographic (2-dimensional and 3-dimensional) and Histologic Findings of Periapical Lesions Treated with Apical Surgery.

INTRODUCTION: The aim of this study was to evaluate the concordance of 2- and 3-dimensional radiography and histopathology in the diagnosis of periapical lesions. METHODS: Patients were consecutively enrolled in this study provided that preoperative periapical radiography (PR) and cone-beam computed tomographic imaging of the tooth to be treated with apical surgery were performed. The periapical lesional tissue was histologically analyzed by 2 blinded examiners. The final histologic diagnosis was compared with the radiographic assessments of 4 blinded observers. The initial study material included 62 teeth in the same number of patients. RESULTS: Four lesions had to be excluded during processing, resulting in a final number of 58 evaluated cases (31 women and 27 men, mean age = 55 years). The final histologic diagnosis of the periapical lesions included 55 granulomas (94.8%) and 3 cysts (5.2%). Histologic analysis of the tissue samples from the apical lesions exhibited an almost perfect agreement between the 2 experienced investigators with an overall agreement of 94.83% (kappa = 0.8011). Radiographic assessment overestimated cysts by 28.4% (cone-beam computed tomographic imaging) and 20.7% (periapical radiography), respectively. Comparing the correlation of the radiographic diagnosis of 4 observers with the final histologic diagnosis, 2-dimensional (kappa = 0.104) and 3-dimensional imaging (kappa = 0.111) provided only minimum agreement. CONCLUSIONS: To establish a final diagnosis of an apical radiolucency, the tissue specimen should be evaluated histologically and specified as a granuloma (with/without epithelium) or a cyst. Analysis of 2-dimensional and 3-dimensional radiographic images alike results only in a tentative diagnosis that should be confirmed with biopsy.

Different Effects of BORIS/CTCFL on Stemness Gene Expression, Sphere Formation and Cell Survival in Epithelial Cancer Stem Cells.

Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites) or CTCFL (CTCF-like) is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients. We have previously shown an association of BORIS-expressing cells with stemness gene expression in embryonic cancer cells. Here, we studied the role of BORIS in epithelial tumor cells. Using BORIS-molecular beacon that was already validated, we were able to show the presence of BORIS mRNA in cancer stem cell-enriched populations (side population and spheres) of cervical, colon and breast tumor cells. BORIS silencing studies showed a decrease of sphere formation capacity in breast and colon tumor cells. Importantly, BORIS-silencing led to down-regulation of hTERT, stem cell (NANOG, OCT4, SOX2 and BMI1) and cancer stem cell markers (ABCG2, CD44 and ALDH1) genes. Conversely, BORIS-induction led to up-regulation of the same genes. These phenotypes were observed in cervical, colon and invasive breast tumor cells. However, a completely different behavior was observed in the non-invasive breast tumor cells (MCF7). Indeed, these cells acquired an epithelial mesenchymal transition phenotype after BORIS silencing. Our results demonstrate that BORIS is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells.

Radio continuum and near-infrared study of the MGRO J2019+37 region

MGRO J2019+37 is an unidentified extended source of very high energy gamma-rays originally reported by the Milagro Collaboration as the brightest TeV source in the Cygnus region. Its extended emission could be powered by either a single or several sources. The GeV pulsar AGL J2020.5+3653 , discovered by AGILE and associated with PSR J2021+3651 , could contribute to the emission from MGRO J2019+37 . Aims. Our aim is to identify radio and near-infrared sources in the field of the extended TeV source MGRO J2019+37 , and study potential counterparts to explain its emission. Methods. We surveyed a region of about 6 square degrees with the Giant Metrewave Radio Telescope (GMRT) at the frequency 610 MHz. We also observed the central square degree of this survey in the near-infrared -band using the 3.5 m telescope in Calar Alto. Archival X-ray observations of some specific fields are included. VLBI observations of an interesting radio source were performed. We explored possible scenarios to produce the multi-TeV emission from MGRO J2019+37 and studied which of the sources could be the main particle accelerator. Results. We present a catalogue of 362 radio sources detected with the GMRT in the field of MGRO J2019+37 , and the results of a cross-correlation of this catalog with one obtained at near-infrared wavelengths, which contains ~3105 sources, as well as with available X-ray observations of the region. Some peculiar sources inside the ~1° uncertainty region of the TeV emission from MGRO J2019+37 are discussed in detail, including the pulsar PSR J2021+3651 and its pulsar wind nebula PWN G75.2+0.1 , two new radio-jet sources, the H II region Sh 2-104 containing two star clusters, and the radio source NVSS J202032+363158 . We also find that the hadronic scenario is the most likely in case of a single accelerator, and discuss the possible contribution from the sources mentioned above. Conclusions. Although the radio and GeV pulsar PSR J2021+3651 / AGL J2020.5+3653 and its associated pulsar wind nebula PWN G75.2+0.1 can contribute to the emission from MGRO J2019+37 , extrapolation of the GeV spectrum does not explain the detected multi-TeV flux. Other sources discussed here could contribute to the emission of the Milagro source.

Lifetime enhancement of scroll rings by spatiotemporal fluctuations

The dynamics of three-dimensional scroll rings with spatiotemporal random excitability is investigated numerically using the FitzHugh-Nagumo model. Depending on the correlation time and length scales of the fluctuations, the lifetime of the ring filament is enlarged and a resonance effect between the time scale of the scroll ring and the time correlation of the noise is observed. Numerical results are interpreted in terms of a simplified stochastic model derived from the kinematical equations for three-dimensional excitable waves.

Lifetime enhancement of scroll rings by spatiotemporal fluctuations

The dynamics of three-dimensional scroll rings with spatiotemporal random excitability is investigated numerically using the FitzHugh-Nagumo model. Depending on the correlation time and length scales of the fluctuations, the lifetime of the ring filament is enlarged and a resonance effect between the time scale of the scroll ring and the time correlation of the noise is observed. Numerical results are interpreted in terms of a simplified stochastic model derived from the kinematical equations for three-dimensional excitable waves.

Adaptation of a Gaussia princeps Luciferase reporter system in Candida albicans for in vivo detection in the Galleria mellonella infection model.

For the past 10 years, mini-host models and in particular the greater wax moth Galleria mellonella have tended to become a surrogate for murine models of fungal infection mainly due to cost, ethical constraints and ease of use. Thus, methods to better assess the fungal pathogenesis in G. mellonella need to be developed. In this study, we implemented the detection of Candida albicans cells expressing the Gaussia princeps luciferase in its cell wall in infected larvae of G. mellonella. We demonstrated that detection and quantification of luminescence in the pulp of infected larvae is a reliable method to perform drug efficacy and C. albicans virulence assays as compared to fungal burden assay. Since the linearity of the bioluminescent signal, as compared to the CFU counts, has a correlation of R(2) = 0.62 and that this method is twice faster and less labor intensive than classical fungal burden assays, it could be applied to large scale studies. We next visualized and followed C. albicans infection in living G. mellonella larvae using a non-toxic and water-soluble coelenterazine formulation and a CCD camera that is commonly used for chemoluminescence signal detection. This work allowed us to follow for the first time C. albicans course of infection in G. mellonella during 4 days.

Evolution of T1 Relaxation, ADC, and Fractional Anisotropy during Early Brain Maturation: A Serial Imaging Study on Preterm Infants.

BACKGROUND AND PURPOSE: The alteration of brain maturation in preterm infants contributes to neurodevelopmental disabilities during childhood. Serial imaging allows understanding of the mechanisms leading to dysmaturation in the preterm brain. The purpose of the present study was to provide reference quantitative MR imaging measures across time in preterm infants, by using ADC, fractional anisotropy, and T1 maps obtained by using the magnetization-prepared dual rapid acquisition of gradient echo technique. MATERIALS AND METHODS: We included preterm neonates born at <30 weeks of gestational age without major brain lesions on early cranial sonography and performed 3 MRIs (3T) from birth to term-equivalent age. Multiple measurements (ADC, fractional anisotropy, and T1 relaxation) were performed on each examination in 12 defined white and gray matter ROIs. RESULTS: We acquired 107 MRIs (35 early, 33 intermediary, and 39 at term-equivalent age) in 39 cerebral low-risk preterm infants. Measures of T1 relaxation time showed a gradual and significant decrease with time in a region- and hemispheric-specific manner. ADC values showed a similar decline with time, but with more variability than T1 relaxation. An increase of fractional anisotropy values was observed in WM regions and inversely a decrease in the cortex. CONCLUSIONS: The gradual change with time reflects the progressive maturation of the cerebral microstructure in white and gray matter. Our study provides reference trajectories from 25 to 40 weeks of gestation of T1 relaxation, ADC, and fractional anisotropy values in low-risk preterm infants. We speculate that deviation thereof might reflect disturbed cerebral maturation; the correlation of this disturbed maturation with neurodevelopmental outcome remains to be addressed.

Radio continuum and near-ingrared study of the MGRO J2019+37 region

Context. MGRO J2019+37 is an unidentified extended source of very high energy gamma-rays originally reported by the Milagro Collaboration as the brightest TeV source in the Cygnus region. Its extended emission could be powered by either a single or several sources. The GeV pulsar AGL J2020.5+3653, discovered by AGILE and associated with PSR J2021+3651, could contribute to the emission from MGRO J2019+37. Our aim is to identify radio and near-infrared sources in the field of the extended TeV source MGRO J2019+37, and study potential counterparts to explain its emission. Methods: We surveyed a region of about 6 square degrees with the Giant Metrewave Radio Telescope (GMRT) at the frequency 610 MHz. We also observed the central square degree of this survey in the near-infrared Ks-band using the 3.5 m telescope in Calar Alto. Archival X-ray observations of some specific fields are included. VLBI observations of an interesting radio source were performed. We explored possible scenarios to produce the multi-TeV emission from MGRO J2019+37 and studied which of the sources could be the main particle accelerator. Results: We present a catalogue of 362 radio sources detected with the GMRT in the field of MGRO J2019+37, and the results of a cross-correlation of this catalog with one obtained at near-infrared wavelengths, which contains ∼3 × 105 sources, as well as with available X-ray observations of the region. Some peculiar sources inside the ∼1◦ uncertainty region of the TeV emission from MGRO J2019+37 are discussed in detail, including the pulsar PSR J2021+3651 and its pulsar wind nebula PWN G75.2+0.1, two new radio-jet sources, the Hii region Sh 2-104 containing two star clusters, and the radio source NVSS J202032+363158. We also find that the hadronic scenario is the most likely in case of a single accelerator, and discuss the possible contribution from the sources mentioned above. Conclusions: Although the radio and GeV pulsar PSR J2021+3651 / AGL J2020.5+3653 and its associated pulsar wind nebula PWN G75.2+0.1 can contribute to the emission from MGRO J2019+37, extrapolation of the GeV spectrum does not explain the detected multi-TeV flux. Other sources discussed here could contribute to the emission of the Milagro source

CFD simulation of complex phenomena containing suspensions and flow throughporous media

There is an increasing reliance on computers to solve complex engineering problems. This is because computers, in addition to supporting the development and implementation of adequate and clear models, can especially minimize the financial support required. The ability of computers to perform complex calculations at high speed has enabled the creation of highly complex systems to model real-world phenomena. The complexity of the fluid dynamics problem makes it difficult or impossible to solve equations of an object in a flow exactly. Approximate solutions can be obtained by construction and measurement of prototypes placed in a flow, or by use of a numerical simulation. Since usage of prototypes can be prohibitively time-consuming and expensive, many have turned to simulations to provide insight during the engineering process. In this case the simulation setup and parameters can be altered much more easily than one could with a real-world experiment. The objective of this research work is to develop numerical models for different suspensions (fiber suspensions, blood flow through microvessels and branching geometries, and magnetic fluids), and also fluid flow through porous media. The models will have merit as a scientific tool and will also have practical application in industries. Most of the numerical simulations were done by the commercial software, Fluent, and user defined functions were added to apply a multiscale method and magnetic field. The results from simulation of fiber suspension can elucidate the physics behind the break up of a fiber floc, opening the possibility for developing a meaningful numerical model of the fiber flow. The simulation of blood movement from an arteriole through a venule via a capillary showed that the model based on VOF can successfully predict the deformation and flow of RBCs in an arteriole. Furthermore, the result corresponds to the experimental observation illustrates that the RBC is deformed during the movement. The concluding remarks presented, provide a correct methodology and a mathematical and numerical framework for the simulation of blood flows in branching. Analysis of ferrofluids simulations indicate that the magnetic Soret effect can be even higher than the conventional one and its strength depends on the strength of magnetic field, confirmed experimentally by Völker and Odenbach. It was also shown that when a magnetic field is perpendicular to the temperature gradient, there will be additional increase in the heat transfer compared to the cases where the magnetic field is parallel to the temperature gradient. In addition, the statistical evaluation (Taguchi technique) on magnetic fluids showed that the temperature and initial concentration of the magnetic phase exert the maximum and minimum contribution to the thermodiffusion, respectively. In the simulation of flow through porous media, dimensionless pressure drop was studied at different Reynolds numbers, based on pore permeability and interstitial fluid velocity. The obtained results agreed well with the correlation of Macdonald et al. (1979) for the range of actual flow Reynolds studied. Furthermore, calculated results for the dispersion coefficients in the cylinder geometry were found to be in agreement with those of Seymour and Callaghan.

Prediction of Antibacterial Activity from Physicochemical Properties of Antimicrobial Peptides

Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible correlation of these with the in vivo onset of activity have only recently been proposed. In addition, such thresholds observed in model membranes occur at local peptide concentrations close to full membrane coverage. In this work we fully develop an interaction model of antimicrobial peptides with biological membranes; by exploring the consequences of the underlying partition formalism we arrive at a relationship that provides antibacterial activity prediction from two biophysical parameters: the affinity of the peptide to the membrane and the critical bound peptide to lipid ratio. A straightforward and robust method to implement this relationship, with potential application to high-throughput screening approaches, is presented and tested. In addition, disruptive thresholds in model membranes and the onset of antibacterial peptide activity are shown to occur over the same range of locally bound peptide concentrations (10 to 100 mM), which conciliates the two types of observations

Role and Function of c-Jun Protein Complex in Cancer Cell Behavior

Transcription factors play a crucial role in the regulation of cell behavior by modulating gene expression profiles. Previous studies have described a dual role for the AP-1 family transcription factor c-Jun in the regulation of cellular fate. In various cell types weak and transient activations of c-Jun N-terminal kinase (JNK) and c-Jun appear to contribute to proliferation and survival, whereas strong and prolonged activation of JNK and c-Jun result in apoptosis. These opposite roles played by c-Jun are cell type specific and the molecular mechanisms defining these antonymous c-Jun-mediated responses remain incompletely understood. c-Jun activity in transformed cells is regulated by signalling cascades downstream of oncoproteins such as Ras and Raf. In addition, the pro-proliferative role and the survival promoting function for c-Jun has been described in various cancer models. Furthermore, c-Jun was described to be overexpressed in different cancer types. However, the molecular mechanisms by which c-Jun exerts these oncogenic functions are not all clearly established. Therefore it is of primary interest to further identify molecular mechanisms and functions for c-Jun in cancer. Regulation of gene expression is tightly dependent on accurate protein-protein interactions. Therefore, co-factors for c-Jun may define the functions for c-Jun in cancer. Identification of protein-protein interactions promoting cancer may provide novel possibilities for cancer treatment. In this study, we show that DNA topoisomerase I (TopoI) is a transcriptional co-factor for c-Jun. Moreover, c-Jun and TopoI together promote expression of epidermal growth factor receptor (EGFR) in cancer cells. We also show that the clinically used TopoI inhibitor topotecan reduces EGFR expression. Importantly, the effect of TopoI on EGFR transcription was shown to depend on c-Jun as Jun-/- cells or cells treated with JNK inhibitor SP600125 are resistant to topotecan treatment both in regulation of EGFR expression and cell proliferation. Moreover, c-Jun regulates the nucleolar localization and the function of the ribonucleic acid (RNA) helicase DDX21, a previously identified member of c-Jun protein complex. In addition, c-Jun stimulates rRNA processing by supporting DDX21 rRNA binding. Finally, this study characterizes a DDX21 dependent expression of cyclin dependent kinase (Cdk) 6, a correlation of DDX21 expression with prostate cancer progression and a substrate binding dependency of DDX21 nucleolar localization in prostate cancer cells. Taken together, the results of this study validate the c-Jun-TopoI interaction and precise the c-Jun-DDX21 interaction. Moreover, these results show the importance for protein-protein interaction in the regulation of their cellular functions in cancer cell behavior. Finally, the results presented here disclose new exciting therapeutic opportunities for cancer treatment.

Active tectonics of the Alhama de Murcia fault, Betic Cordillera, Spain

We present an overview of the knowledge of the structure and the seismic behavior of the Alhama de Murcia Fault (AMF). We utilize a fault traces map created from a LIDAR DEM combined with the geodynamic setting, the analysis of the morphology, the distribution of seismicity, the geological information from E 1:50000 geological maps and the available paleoseismic data to describe the recent activity of the AMF. We discuss the importance of uncertainties regarding the structure and kinematics of the AMF applied to the interpretation and spatial correlation of the paleoseismic data. In particular, we discuss the nature of the faults dipping to the SE (antithetic to the main faults of the AMF) in several segments that have been studied in the previous paleoseismic works. A special chapter is dedicated to the analysis of the tectonic source of the Lorca 2011 earthquake that took place in between two large segments of the fault.

Tautomerism and Fragmentation of Biologically Active Hetero Atom (O, N)-Containing Acyclic and Cyclic Compounds Under Electron Ionization

In this thesis a total of 86 compounds containing the hetero atoms oxygen and nitrogen were studied under electron ionization mass spectrometry (EIMS). These compounds are biologically active and were synthesized by various research groups. The main attention of this study was paid on the fragmentations related to different tautomeric forms of 2- phenacylpyridines, 2-phenacylquinolines, 8-aryl-3,4-dioxo-2H,8H-6,7-dihydroimidazo- [2,1-c][1,2,4]triazines and aryl- and benzyl-substituted 2,3-dihydroimidazo[1,2-a]pyrimidine-5,7-(1H,6H)-diones. Also regio/stereospecific effects on fragmentations of pyrrolo- and isoindoloquinazolinones and naphthoxazine, naphthpyrrolo-oxazinone and naphthoxazino-benzoxazine derivatives were screened. Results were compared with NMR data, when available. The first part of thesis consists of theory and literature review of different types of tautomerism and fragmentation mechanisms in EIMS. The effects of tautomerism in biological systems are also briefly reviewed. In the second part of the thesis the own results of the author, based on six publications,are discussed. For 2-phenacylpyridines and 2-phenacylquinolines the correlation of different Hammett substituent constants to the relative abundances (RA) or total ion currents (% TIC) of selected ions were investigated. Although it was not possible to assign most of the ions formed unambiguously to the different tautomers, the linear fits of their RAs and % TICs can be related to changing contributions of different tautomeric forms. For dioxoimidazotriazines and imidazopyrimidinediones the effects of substituents were rather weak. The fragmentations were also found useful for obtaining structural information. Some stereoisomeric pairs of pyrrolo- and isoindoloquinazolines and regiomeric pairs of naphtoxazine derivatives showed clear differences in thir mass spectra. Some mechanisms are suggested for their fragmentations.

20 Myr of eccentricity paced lacustrine cycles in the Cenozoic Ebro Basin

Long-period orbital forcing is a crucial component of the major global climate shifts during the Cenozoic as revealed in marine pelagic records. A complementary regional perspective of climate change can be assessed from internally drained lake basins, which are directly affected by insolation and precipitation balance. The Ebro Basin in northeastern Iberia embraces a 20 Myr long continuous sedimentary record where recurrent expansions and retractions of the central lacustrine system suggest periodic shifts of water balance due to orbital oscillations. In order to test climatic (orbital) forcing a key-piece of the basin, the Los Monegros lacustrine system, has been analyzed in detail. The cyclostratigraphic analysis points to orbital eccentricity as pacemaker of short to long-term lacustrine sequences, and reveals a correlation of maxima of the 100-kyr, 400-kyr and 2.4-Myr eccentricity cycles with periods of lake expansion. A magnetostratigraphy-based chronostratigraphy of the complete continental record allows further assessing long-period orbital forcing at basin scale, a view that challenges alternate scenarios where the stratigraphic architecture in foreland systems is preferably associated to tectonic processes. We conclude that while the location of lacustrine depocenters reacted to the long-term tectonic-driven accommodation changes, shorter wavelenght oscillations of lake environments, still million-year scale, claims for a dominance of orbital forcing. We suggest a decoupling between (tectonic) supply-driven clastic sequences fed from basin margins and (climatic) base level-driven lacustrine sequences in active settings with medium to large sediment transfer systems.