Search for first harmonic modulation in the right ascension distribution of cosmic rays detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above 2.5 x 10(17) eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% C.L. for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations. (C) 2011 Elsevier B.V. All rights reserved.

Low-complexity BCH codes with optimized interleavers for DQPSK systems with laser phase noise

The presence of high phase noise in addition to additive white Gaussian noise in coherent optical systems affects the performance of forward error correction (FEC) schemes. In this paper, we propose a simple scheme for such systems, using block interleavers and binary Bose–Chaudhuri–Hocquenghem (BCH) codes. The block interleavers are specifically optimized for differential quadrature phase shift keying modulation. We propose a method for selecting BCH codes that, together with the interleavers, achieve a target post-FEC bit error rate (BER). This combination of interleavers and BCH codes has very low implementation complexity. In addition, our approach is straightforward, requiring only short pre-FEC simulations to parameterize a model, based on which we select codes analytically. We aim to correct a pre-FEC BER of around (Formula presented.). We evaluate the accuracy of our approach using numerical simulations. For a target post-FEC BER of (Formula presented.), codes selected using our method result in BERs around 3(Formula presented.) target and achieve the target with around 0.2 dB extra signal-to-noise ratio.

Impact of optical phase conjugation on the nonlinear Shannon limit

Compensation of the detrimental impacts of nonlinearity on long-haul wavelength division multiplexed system performance is discussed, and the difference between transmitter, receiver and in-line compensation analyzed. We demonstrate that ideal compensation of nonlinear noise could result in an increase in the signal-to-noise ratio (measured in dB) of 50%, and that reaches may be more than doubled for higher order modulation formats. The influence of parametric noise amplification is discussed in detail, showing how increased numbers of optical phase conjugators may further increase the received signal-tonoise ratio. Finally the impact of practical real world system imperfections, such as polarization mode dispersion, are outlined.

A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer

An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine

Modulateurs intégrés sur silicium pour la transmission de signaux à modulation d'amplitude multi-niveau

Au cours des dernières années, la photonique intégrée sur silicium a progressé rapidement. Les modulateurs issus de cette technologie présentent des caractéristiques potentiellement intéressantes pour les systèmes de communication à courte portée. En effet, il est prévu que ces modulateurs pourront être opérés à des vitesses de transmission élevées, tout en limitant le coût de fabrication et la consommation de puissance. Parallèlement, la modulation d’amplitude multi-niveau (PAM) est prometteuse pour ce type de systèmes. Ainsi, ce travail porte sur le développement de modulateurs de silicium pour la transmission de signaux PAM. Dans le premier chapitre, les concepts théoriques nécessaires à la conception de modulateurs de silicium sont présentés. Les modulateurs Mach-Zehnder et les modulateurs à base de réseau de Bragg sont principalement abordés. De plus, les effets électro-optiques dans le silicium, la modulation PAM, les différents types d’électrodes intégrées et la compensation des distorsions par traitement du signal sont détaillés.Dans le deuxième chapitre, un modulateur Mach-Zehnder aux électrodes segmentées est présenté. La segmentation des électrodes permet la génération de signaux optiques PAM à partir de séquences binaires. Cette approche permet d’éliminer l’utilisation de convertisseur numérique-analogique en intégrant cette fonction dans le domaine optique, ce qui vise à réduire le coût du système de communication. Ce chapitre contient la description détaillée du modulateur, les résultats de caractérisation optique et de la caractérisation électrique, ainsi que les tests systèmes. De plus, les tests systèmes incluent l’utilisation de pré-compensation ou de post-compensation du signal sous la forme d’égalisation de la réponse en fréquence pour les formats de modulation PAM-4 et PAM-8 à différents taux binaires. Une vitesse de transmission de 30 Gb/s est démontrée dans les deux cas et ce malgré une limitation importante de la réponse en fréquence suite à l’ajout d’un assemblage des circuits radiofréquences (largeur de bande 3 dB de 8 GHz). Il s’agit de la première démonstration de modulation PAM-8 à l’aide d’un modulateur Mach-Zehnder aux électrodes segmentées. Finalement, les conclusions tirées de ce travail ont mené à la conception d’un deuxième modulateur Mach-Zehnder aux électrodes segmentées présentement en phase de test, dont les performances montrent un très grand potentiel. Dans le troisième chapitre, un modulateur à réseau de Bragg à deux sauts de phase est présenté. L’utilisation de réseaux de Bragg est une approche encore peu développée pour la modulation. En effet, la réponse spectrale de ces structures peut être contrôlée précisément, une caractéristique intéressante pour la conception de modulateurs. Dans ces travaux, nous proposons l’ajout de deux sauts de phase à un réseau de Bragg uniforme pour obtenir un pic de transmission dans la bande de réflexion de celui-ci. Ainsi, il est possible d’altérer l’amplitude du pic de transmission à l’aide d’une jonction pn. Comme pour le deuxième chapitre, ce chapitre inclut la description détaillée du modulateur, les résultats des caractérisations optique et électrique, ainsi que les tests systèmes. De plus, la caractérisation de jonctions pn à l’aide du modulateur à réseau de Bragg est expliquée. Des vitesses de transmission PAM-4 de 60 Gb/s et OOK de 55 Gb/s sont démontrées après la compensation des distorsions des signaux. À notre connaissance, il s’agit du modulateur à réseau de Bragg le plus rapide à ce jour. De plus, pour la première fois, les performances d’un tel modulateur s’approchent de celles des modulateurs de silicium les plus rapides utilisant des microrésonateurs en anneau ou des interféromètres Mach-Zehnder.

Acousto-optic modulation of optical reflection properties in fiber Bragg gratings and the application in fiber lasers

This thesis aims to investigate the interaction of acoustic waves and fiber Bragg gratings (FBGs) in standard and suspended-core fibers (SCFs), to evaluate the influence of the fiber, grating and modulator design on the increase of the modulation efficiency, bandwidth and frequency. Initially, the frequency response and the resonant acoustic modes of a low frequency acousto-optic modulator (f < 1.2 MHz) are numerically investigated by using the finite element method. Later, the interaction of longitudinal acoustic waves and FBGs in SCFs is also numerically investigated. The fiber geometric parameters are varied and the strain and grating properties are simulated by means of the finite element method and the transfer matrix method. The study indicates that the air holes composing the SCF cause a significant reduction of the amount of silica in the fiber cross section increasing acousto-optic interaction in the core. Experimental modulation of the reflectivity of FBGs inscribed in two distinct SCFs indicates evidences of this increased interaction. Besides, a method to acoustically induce a dynamic phase-shift in a chirped FBG employing an optimized design of modulator is shown. Afterwards, a combination of this modulator and a FBG inscribed in a three air holes SCF is applied to mode-lock an ytterbium doped fiber laser. To improve the modulator design for future applications, two other distinct devices are investigated to increase the acousto-optic interaction, bandwidth and frequency (f > 10 MHz). A high reflectivity modulation has been achieved for a modulator based on a tapered fiber. Moreover, an increased modulated bandwidth (320 pm) has been obtained for a modulator based on interaction of a radial long period grating (RLPG) and a FBG inscribed in a standard fiber. In summary, the results show a considerable reduction of the grating/fiber length and the modulator size, indicating possibilities for compact and faster acousto-optic fiber devices. Additionally, the increased interaction efficiency, modulated bandwidth and frequency can be useful to shorten the pulse width of future all-fiber mode-locked fiber lasers, as well, to other photonic devices which require the control of the light in optical fibers by electrically tunable acoustic waves.

Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy.

We apply wide-field interferometric microscopy techniques to acquire quantitative phase profiles of ventricular cardiomyocytes in vitro during their rapid contraction with high temporal and spatial resolution. The whole-cell phase profiles are analyzed to yield valuable quantitative parameters characterizing the cell dynamics, without the need to decouple thickness from refractive index differences. Our experimental results verify that these new parameters can be used with wide field interferometric microscopy to discriminate the modulation of cardiomyocyte contraction dynamics due to temperature variation. To demonstrate the necessity of the proposed numerical analysis for cardiomyocytes, we present confocal dual-fluorescence-channel microscopy results which show that the rapid motion of the cell organelles during contraction preclude assuming a homogenous refractive index over the entire cell contents, or using multiple-exposure or scanning microscopy.

Multi-phase electric drives for mobility

Multi-phase electrical drives are potential candidates for the employment in innovative electric vehicle powertrains, in response to the request for high efficiency and reliability of this type of application. In addition to the multi-phase technology, in the last decades also, multilevel technology has been developed. These two technologies are somewhat complementary since both allow increasing the power rating of the system without increasing the current and voltage ratings of the single power switches of the inverter. In this thesis, some different topics concerning the inverter, the motor and the fault diagnosis of an electric vehicle powertrain are addressed. In particular, the attention is focused on multi-phase and multilevel technologies and their potential advantages with respect to traditional technologies. First of all, the mathematical models of two multi-phase machines, a five-phase induction machine and an asymmetrical six-phase permanent magnet synchronous machines are developed using the Vector Space Decomposition approach. Then, a new modulation technique for multi-phase multilevel T-type inverters, which solves the voltage balancing problem of the DC-link capacitors, ensuring flexible management of the capacitor voltages, is developed. The technique is based on the proper selection of the zero-sequence component of the modulating signals. Subsequently, a diagnostic technique for detecting the state of health of the rotor magnets in a six-phase permanent magnet synchronous machine is established. The technique is based on analysing the electromotive force induced in the stator windings by the rotor magnets. Furthermore, an innovative algorithm able to extend the linear modulation region for five-phase inverters, taking advantage of the multiple degrees of freedom available in multi-phase systems is presented. Finally, the mathematical model of an eighteen-phase squirrel cage induction motor is defined. This activity aims to develop a motor drive able to change the number of poles of the machine during the machine operation.

Multi-functional electrocatalysts for CO2 reduction reaction: towards the modulation of selectivity

The electrocatalytic reduction of CO2 (CO2RR) is a captivating strategy for the conversion of CO2 into fuels, to realize a carbon neutral circular economy. In the recent years, research has focused on the development of new materials and technology capable of capturing and converting CO2 into useful products. The main problem of CO2RR is given by its poor selectivity, which can lead to the formation of numerous reaction products, to the detriment of efficiencies. For this reason, the design of new electrocatalysts that selectively and efficiently reduce CO2 is a fundamental step for the future exploitation of this technology. Here we present a new class of electrocatalysts, designed with a modular approach, namely, deriving from the combination of different building blocks in a single nanostructure. With this approach it is possible to obtain materials with an innovative design and new functionalities, where the interconnections between the various components are essential to obtain a highly selective and efficient reduction of CO2, thus opening up new possibilities in the design of optimized electrocatalytic materials. By combining the unique physic-chemical properties of carbon nanostructures (CNS) with nanocrystalline metal oxides (MO), we were able to modulate the selectivity of CO2RR, with the production of formic acid and syngas at low overpotentials. The CNS have not only the task of stabilizing the MO nanoparticles, but the creation of an optimal interface between two nanostructures is able to improve the catalytic activity of the active phase of the material. While the presence of oxygen atoms in the MO creates defects that accelerate the reaction kinetics and stabilize certain reaction intermediates, selecting the reaction pathway. Finally, a part was dedicated to the study of the experimental parameters influencing the CO2RR, with the aim of improving the experimental setup in order to obtain commercial catalytic performances.

Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Chemical Immobilization Of Crosslinked Polymeric Ionic Liquids On Nitinol Wires Produces Highly Robust Sorbent Coatings For Solid-phase Microextraction.

Super elastic nitinol (NiTi) wires were exploited as highly robust supports for three distinct crosslinked polymeric ionic liquid (PIL)-based coatings in solid-phase microextraction (SPME). The oxidation of NiTi wires in a boiling (30%w/w) H2O2 solution and subsequent derivatization in vinyltrimethoxysilane (VTMS) allowed for vinyl moieties to be appended to the surface of the support. UV-initiated on-fiber copolymerization of the vinyl-substituted NiTi support with monocationic ionic liquid (IL) monomers and dicationic IL crosslinkers produced a crosslinked PIL-based network that was covalently attached to the NiTi wire. This alteration alleviated receding of the coating from the support, which was observed for an analogous crosslinked PIL applied on unmodified NiTi wires. A series of demanding extraction conditions, including extreme pH, pre-exposure to pure organic solvents, and high temperatures, were applied to investigate the versatility and robustness of the fibers. Acceptable precision of the model analytes was obtained for all fibers under these conditions. Method validation by examining the relative recovery of a homologous group of phthalate esters (PAEs) was performed in drip-brewed coffee (maintained at 60 °C) by direct immersion SPME. Acceptable recoveries were obtained for most PAEs in the part-per-billion level, even in this exceedingly harsh and complex matrix.

Multitarget Effects Of Quercetin In Leukemia.

This study proposes to investigate quercetin antitumor efficacy in vitro and in vivo, using the P39 cell line as a model. The experimental design comprised leukemic cells or xenografts of P39 cells, treated in vitro or in vivo, respectively, with quercetin; apoptosis, cell-cycle and autophagy activation were then evaluated. Quercetin caused pronounced apoptosis in P39 leukemia cells, followed by Bcl-2, Bcl-xL, Mcl-1 downregulation, Bax upregulation, and mitochondrial translocation, triggering cytochrome c release and caspases activation. Quercetin also induced the expression of FasL protein. Furthermore, our results demonstrated an antioxidant activity of quercetin. Quercetin treatment resulted in an increased cell arrest in G1 phase of the cell cycle, with pronounced decrease in CDK2, CDK6, cyclin D, cyclin E, and cyclin A proteins, decreased Rb phosphorylation and increased p21 and p27 expression. Quercetin induced autophagosome formation in the P39 cell line. Autophagy inhibition induced by quercetin with chloroquine triggered apoptosis but did not alter quercetin modulation in the G1 phase. P39 cell treatment with a combination of quercetin and selective inhibitors of ERK1/2 and/or JNK (PD184352 or SP600125, respectively), significantly decreased cells in G1 phase, this treatment, however, did not change the apoptotic cell number. Furthermore, in vivo administration of quercetin significantly reduced tumor volume in P39 xenografts and confirmed in vitro results regarding apoptosis, autophagy, and cell-cycle arrest. The antitumor activity of quercetin both in vitro and in vivo revealed in this study, point to quercetin as an attractive antitumor agent for hematologic malignancies.

Elevated Cetp Activity During Acute Phase Of Myocardial Infarction Is Independently Associated With Endothelial Dysfunction And Adverse Clinical Outcome.

Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). Consecutive patients with STEMI (n = 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p = 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r = 0.72; p = 0.014) and FMD (r = -0.61; p = 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p = 0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p = 0.044). An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.

Down-regulation Of Slc8a1 As A Putative Apoptosis-evasion Mechanism By Modulation Of Calcium Levels In Penile Carcinoma.

The SLC8A1 gene, which encodes the Na(+)/Ca(2+) exchanger, plays a key role in calcium homeostasis. Our previous gene expression oligoarray data revealed SLC8A1 underexpression in penile carcinoma (PeCa). The aim of this study was to investigate whether the dysregulation of SLC8A1 expression is associated with apoptosis and cell proliferation in PeCa, via modulation of calcium concentration. The underlying mechanisms of SLC8A1 underexpression were also explored, focusing on copy number alteration and microRNA. Transcript levels of SLC8A1 gene and miR-223 were evaluated by quantitative PCR, comparing PeCa samples with normal glans tissues. SLC8A1 copy number was evaluated by microarray-based comparative genomic hybridization (array-CGH). Caspase-3 and Ki-67 immunostaining, as well as calcium distribution by Laser Ablation Imaging Inductively Coupled Plasma Mass Spectrometry [LA(i)-ICP-MS], were investigated in both normal and tumor samples. Confirming our previous data, SLC8A1 underexpression was detected in PeCa samples (P=0.001) and was not associated with gene copy number loss. In contrast, overexpression of miR-223 (P=0.002) was inversely correlated with SLC8A1 (P=0.015, r=-0.426), its putative repressor. In addition, SLC8A1 underexpression was associated with decreased calcium distribution, high Ki-67 and low caspase-3 immunoexpression in PeCa when compared with normal tissues. Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to reduced calcium levels in PeCa and, consequently, to suppression of apoptosis and increased tumor cell proliferation. These data suggest that the miR-223-NCX1-calcium-signaling axis may represent a potential therapeutic approach in PeCa.

Evaluation Of The Location Of Capsules Swallowed With Food During The Pharyngeal Phase Triggering In Asymptomatic Adults.

To assess the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. The location of the bolus during the pharyngeal phase triggering provides information about the sensorimotor model of the beginning of deglutition onset. To evaluate the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. A videofluoroscopy swallowing study was carried out in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years, who were evaluated with hard gelatin capsules #00 and #3 containing barium sulfate, swallowed with liquid food and pudding, in free volume. The first laryngeal elevation movement was the criterion to locate the pharyngeal phase triggering. Statistical analysis was based on the McNemar test. Capsule #3 presented higher percentage of location in the tongue dorsum compared to capsule #00, and capsule #00 presented higher percentage of location in the tongue base and vallecula compared to capsule #3. There was a difference between different capsules swallowed with liquid (p=0.016) and pudding (p=0.037). The capsule size influenced the location of the pharyngeal phase triggering. Smaller capsules started pharyngeal phase in the most anterior region (tongue dorsum) compared to larger capsules.