Cut Out By The Middle Man: The Free Speech Implications Of Social Network Blocking and Banning In The EU

This article examines social network users’ legal defences against content removal under the EU and ECHR frameworks, and their implications for the effective exercise of free speech online. A review of the Terms of Use and content moderation policies of two major social network services, Facebook and Twitter, shows that end users are unlikely to have a contractual defence against content removal. Under the EU and ECHR frameworks, they may demand the observance of free speech principles in state-issued blocking orders and their implementation by intermediaries, but cannot invoke this ‘fair balance’ test against the voluntary removal decisions by the social network service. Drawing on practical examples, this article explores the threat to free speech created by this lack of accountability: Firstly, a shift from legislative regulation and formal injunctions to public-private collaborations allows state authorities to influence these ostensibly voluntary policies, thereby circumventing constitutional safeguards. Secondly, even absent state interference, the commercial incentives of social media cannot be guaranteed to coincide with democratic ideals. In light of the blurring of public and private functions in the regulation of social media expression, this article calls for the increased accountability of the social media services towards end users regarding the observance of free speech principles

Evaporation of free water causes concentrational alkalosis in vitro

BACKGROUND The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model. MATERIALS AND METHODS Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson. RESULTS Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well. CONCLUSIONS Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function.

Surface charge of polymer coated SPIONs influences the serum protein adsorption, colloidal stability and subsequent cell interaction in vitro

It is known that the nanoparticle-cell interaction strongly depends on the physicochemical properties of the investigated particles. In addition, medium density and viscosity influence the colloidal behaviour of nanoparticles. Here, we show how nanoparticle-protein interactions are related to the particular physicochemical characteristics of the particles, such as their colloidal stability, and how this significantly influences the subsequent nanoparticle-cell interaction in vitro. Therefore, different surface charged superparamagnetic iron oxide nanoparticles were synthesized and characterized. Similar adsorbed protein profiles were identified following incubation in supplemented cell culture media, although cellular uptake varied significantly between the different particles. However, positively charged nanoparticles displayed a significantly lower colloidal stability than neutral and negatively charged particles while showing higher non-sedimentation driven cell-internalization in vitro without any significant cytotoxic effects. The results of this study strongly indicate therefore that an understanding of the aggregation state of NPs in biological fluids is crucial in regards to their biological interaction(s).

Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.

RATIONALE: Thyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. OBJECTIVES: This study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. METHODS: This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.

The Reform of the EC Audiovisual Media Regulation : Television Without Cultural Diversity

In the profoundly changing and dynamic world of contemporary audiovisual media, what has remained surprisingly unaffected is regulation. In the European Union, the new Audiovisual Media Services Directive (AVMS), proposed by the European Commission on December 13, 2005, should allegedly rectify this situation. Amending the existing Television without Frontiers Directive, it should offer a fresh approach and meet the challenge of appropriately regulating media in a complex environment. It is meant to achieve a balance between the free circulation of TV broadcast and new audiovisual media and the preservation of values of cultural identity and diversity, while respecting the principles of subsidiarity and proportionality inherent to the Community. The purpose of this paper is to examine whether and how the changes envisaged to the EC audiovisual media regime might influence cultural diversity in Europe. It addresses subsequently the question of whether the new AVMS properly safeguards the balance between competition and the public interest in this regard, or whether cultural diversity remains a mere political banner.

Enquiry into the Notion of Cultural Protectionism in the Media and its Dimensions in Cyberspace

Cultural protectionism has been an element of national and foreign policies, as an extension of state sovereignty expressed both in a defensive and offensive manner. While the generic protectionist formula in the sense of restraining trade between states through measures such as import tariffs or quotas and through privileging domestic production has somewhat disintegrated over time under the rationale for free trade and the strong practical evidence of its benefits, the particular case of cultural protectionism has persevered. As we reveal in this paper, however, it has been modified, or at least its rhetoric has changed. The enquiry into the notion of cultural protectionism or cultural diversity, as the current political jargon would have it, is but one of the paper’s objectives. Its second and certainly more ambitious goal is the search for the normative dimensions of cultural diversity policies in the global digital space, asking what adjustments are needed and how feasible the entire project of diversity regulation in this environment may be. Taking into account the specificities of cyberspace and in a forward-looking manner, we propose some adjustments to current media policy practices that could better serve the goal of a sustainably diverse cultural environment.

Development of a high- versus low-pathogenicity model of the free-living amoeba Naegleria fowleri

Species in the genus Naegleria are free-living amoebae of the soil and warm fresh water. Although around 30 species have been recognized, Naegleria fowleri is the only one that causes primary amoebic meningoencephalitis (PAM) in humans. PAM is an acute and fast progressing disease affecting the central nervous system. Most of the patients die within 1-2 weeks of exposure to the infectious water source. The fact that N. fowleri causes such fast progressing and highly lethal infections has opened many questions regarding the relevant pathogenicity factors of the amoeba. In order to investigate the pathogenesis of N. fowleri under defined experimental conditions, we developed a novel high- versus low-pathogenicity model for this pathogen. We showed that the composition of the axenic growth media influenced growth behaviour and morphology, as well as in vitro cytotoxicity and in vivo pathogenicity of N. fowleri. Trophozoites maintained in Nelson's medium were highly pathogenic for mice, demonstrated rapid in vitro proliferation, characteristic expression of surface membrane vesicles and a small cell diameter, and killed target mouse fibroblasts by both contact-dependent and -independent destruction. In contrast, N. fowleri cultured in PYNFH medium exhibited a low pathogenicity, slower growth, increased cell size and contact-dependent target cell destruction. However, cultivation of the amoeba in PYNFH medium supplemented with liver hydrolysate (LH) resulted in trophozoites that were highly pathogenic in mice, and demonstrated an intermediate proliferation rate in vitro, diminished cell diameter and contact-dependent target cell destruction. Thus, in this model, the presence of LH resulted in increased proliferation of trophozoites in vitro and enhanced pathogenicity of N. fowleri in mice. However, neither in vitro cytotoxicity mechanisms nor the presence of membrane vesicles on the surface correlated with the pathologic potential of the amoeba. This indicated that the pathogenicity of N. fowleri remains a complex interaction between as-yet-unidentified cellular mechanisms.

Serum calcification propensity predicts all-cause mortality in predialysis CKD

Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T50 tertile was more than two times the risk among patients in the highest T50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.

Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri.

BACKGROUND The free-living amoeba Naegleria fowleri is the causative agent of the rapidly progressing and typically fatal primary amoebic meningoencephalitis (PAM) in humans. Despite the devastating nature of this disease, which results in > 97% mortality, knowledge of the pathogenic mechanisms of the amoeba is incomplete. This work presents a comparative proteomic approach based on an experimental model in which the pathogenic potential of N. fowleri trophozoites is influenced by the compositions of different media. RESULTS As a scaffold for proteomic analysis, we sequenced the genome and transcriptome of N. fowleri. Since the sequence similarity of the recently published genome of Naegleria gruberi was far lower than the close taxonomic relationship of these species would suggest, a de novo sequencing approach was chosen. After excluding cell regulatory mechanisms originating from different media compositions, we identified 22 proteins with a potential role in the pathogenesis of PAM. Functional annotation of these proteins revealed, that the membrane is the major location where the amoeba exerts its pathogenic potential, possibly involving actin-dependent processes such as intracellular trafficking via vesicles. CONCLUSION This study describes for the first time the 30 Mb-genome and the transcriptome sequence of N. fowleri and provides the basis for the further definition of effective intervention strategies against the rare but highly fatal form of amoebic meningoencephalitis.

PLACENTAL URIC ACID TRANSPORTER GLUT9 IS MODULATED BY FREE IODINE

PLACENTAL URIC ACID TRANSPORTER GLUT9 IS MODULATED BY FREE IODINE Objectives: Materno-fetal transplacental transport is crucial for the fetal well-being. The altered expression of placental transport proteins under specific pathophysiological conditions may affect the intrauterine environment. Pre-eclampsia is often associated with high maternal uric acid serum levels. The regulation of the placental uric transport system and its transporter glucose transporter (GLUT)-9 are not fully understood yet. The aim of this study was to investigate the placental urate transport and to characterize its transporter GLUT9. Methods: In this study we used a transepithelial transport (Transwell®) model to assess uric acid transport activity. Electrophysiological techniques and radioactive ligand up-take assays were used to measure transport activity of GLUT9 expressed in Xenopus oocytes. Results: In the Transwell/model uric acid is transported across the BeWo choriocarcinoma cell monolayer with 530 pmol/min at the linear stage. We could successfully over-express GLUT9 using the Xenopus laevis oocytes expression system. Chloride modulates the urate transport system: interestingly replacing chloride with iodine resulted in a complete loss of urate transport activity.We determined the IC50 of iodine at 30uM concentration. In radioactive up-take experiments iodinehad noeffect on uric acid transport. Conclusions: In vitro the “materno-fetal” transport of uric acid is slow. This indicates that in vivo the child is protected from short-term fluctuations of maternal uric acid serum concentrations. The different results regarding iodine-mediated regulation of GLUT9 transport activity between electrophysiological and radioactive ligand uptake experiments may suggest that iodine does not directly inhibit uric acid transport, but changes the mode of up-take from an electrogenic to an electroneutral transport. GLUT9 is not an uric acid uniporter, there are more ions involved in the transport. This may allow regulating uric acid transport by the change from an active to a passive transport.

Low serum testosterone and increased diastolic ocular perfusion pressure: a risk for retinal microvasculature

BACKGROUND Low levels of testosterone in men and changes in retinal microvascular calibre are both associated with hypertension and cardiovascular disease risk. Sex hormones are also associated with blood flow in microvascular beds which might be a key intermediate mechanism in the development of hypertension. Whether a direct association between endogenous testosterone and retinal microvascular calibre exists is currently unknown. We aimed to determine whether testosterone is independently associated with ocular perfusion via a possible association with retinal vascular calibre or whether it plays only a secondary role via its effect on blood pressure in a bi-ethnic male cohort. PROBANDS AND METHODS A total of 72 black and 81 white men (28-68 years of age) from the follow-up phase of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study were included in this sub-study. Ambulatory pulse pressure and intraocular perfusion pressures were obtained, while metabolic variables and testosterone were measured from fasting venous blood samples. Retinal vascular calibre was quantified from digital photographs using standardised protocols. RESULTS The black men revealed a poorer cardiometabolic profile and higher pulsatile pressure (>50 mm Hg), intraocular pressure and diastolic ocular perfusion pressure than the white men (p≤0.05). Only in the white men was free testosterone positively associated with retinal calibre, i.e. arterio-venular ratio and central retinal arterial calibre and inversely with central retinal venular calibre. These associations were not found in the black men, independent of whether pulse pressure and ocular perfusion pressure were part of the model. CONCLUSIONS These results suggest an independent, protective effect of testosterone on the retinal vasculature where an apparent vasodilatory response in the retinal resistance microvessels was observed in white men.

Optimization of a label-free biosensor vertically characterized based on a periodic lattice of high aspect ratio SU-8 nano-pillars with a simplified 2D theoretical model

We have recently demonstrated a biosensor based on a lattice of SU8 pillars on a 1 μm SiO2/Si wafer by measuring vertically reflectivity as a function of wavelength. The biodetection has been proven with the combination of Bovine Serum Albumin (BSA) protein and its antibody (antiBSA). A BSA layer is attached to the pillars; the biorecognition of antiBSA involves a shift in the reflectivity curve, related with the concentration of antiBSA. A detection limit in the order of 2 ng/ml is achieved for a rhombic lattice of pillars with a lattice parameter (a) of 800 nm, a height (h) of 420 nm and a diameter(d) of 200 nm. These results correlate with calculations using 3D-finite difference time domain method. A 2D simplified model is proposed, consisting of a multilayer model where the pillars are turned into a 420 nm layer with an effective refractive index obtained by using Beam Propagation Method (BPM) algorithm. Results provided by this model are in good correlation with experimental data, reaching a reduction in time from one day to 15 minutes, giving a fast but accurate tool to optimize the design and maximizing sensitivity, and allows analyzing the influence of different variables (diameter, height and lattice parameter). Sensitivity is obtained for a variety of configurations, reaching a limit of detection under 1 ng/ml. Optimum design is not only chosen because of its sensitivity but also its feasibility, both from fabrication (limited by aspect ratio and proximity of the pillars) and fluidic point of view. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Automatic motion compensation of free breathing acquired myocardial perfusion data by using independent component analysis

Images acquired during free breathing using first-pass gadolinium-enhanced myocardial perfusion magnetic resonance imaging (MRI) exhibit a quasiperiodic motion pattern that needs to be compensated for if a further automatic analysis of the perfusion is to be executed. In this work, we present a method to compensate this movement by combining independent component analysis (ICA) and image registration: First, we use ICA and a time?frequency analysis to identify the motion and separate it from the intensity change induced by the contrast agent. Then, synthetic reference images are created by recombining all the independent components but the one related to the motion. Therefore, the resulting image series does not exhibit motion and its images have intensities similar to those of their original counterparts. Motion compensation is then achieved by using a multi-pass image registration procedure. We tested our method on 39 image series acquired from 13 patients, covering the basal, mid and apical areas of the left heart ventricle and consisting of 58 perfusion images each. We validated our method by comparing manually tracked intensity profiles of the myocardial sections to automatically generated ones before and after registration of 13 patient data sets (39 distinct slices). We compared linear, non-linear, and combined ICA based registration approaches and previously published motion compensation schemes. Considering run-time and accuracy, a two-step ICA based motion compensation scheme that first optimizes a translation and then for non-linear transformation performed best and achieves registration of the whole series in 32 ± 12 s on a recent workstation. The proposed scheme improves the Pearsons correlation coefficient between manually and automatically obtained time?intensity curves from .84 ± .19 before registration to .96 ± .06 after registration

Hydrodynamic forces on heave plates for offshore systems oscillating close to the seabed or the free surface

La energía eólica marina es uno de los recursos energéticos con mayor proyección pudiendo contribuir a reducir el consumo de combustibles fósiles y a cubrir la demanda de energía en todo el mundo. El concepto de aerogenerador marino está basado en estructuras fijas como jackets o en plataformas flotantes, ya sea una semisumergible o una TLP. Se espera que la energía eólica offshore juegue un papel importante en el perfil de producción energética de los próximos años; por tanto, las turbinas eólicas deben hacerse más fables y rentables para ser competitivas frente a otras fuentes de energía. Las estructuras flotantes pueden experimentar movimientos resonantes en estados de la mar con largos períodos de oleaje. Estos movimientos disminuyen su operatividad y pueden causar daños en los componentes eléctricos de las turbinas y en las palas, también en los risers y moorings. La respuesta de la componente vertical del movimiento puede reducirse mediante diferentes actuaciones: (1) aumentando la amortiguación del sistema, (2) manteniendo el período del movimiento vertical fuera del rango de la energía de la ola, y (3) reduciendo las fuerzas de excitación verticales. Un ejemplo típico para llevar a cabo esta reducción son las "Heave Plates". Las heave plates son placas que se utilizan en la industria offshore debido a sus características hidrodinámicas, ya que aumentan la masa añadida y la amortiguación del sistema. En un análisis hidrodinámico convencional, se considera una estructura sometida a un oleaje con determinadas características y se evalúan las cargas lineales usando la teoría potencial. El amortiguamiento viscoso, que juega un papel crucial en la respuesta en resonancia del sistema, es un dato de entrada para el análisis. La tesis se centra principalmente en la predicción del amortiguamiento viscoso y de la masa añadida de las heave plates usadas en las turbinas eólicas flotantes. En los cálculos, las fuerzas hidrodinámicas se han obtenido con el f n de estudiar cómo los coeficientes hidrodinámicos de masa añadida5 y amortiguamiento varían con el número de KC, que caracteriza la amplitud del movimiento respecto al diámetro del disco. Por otra parte, se ha investigado la influencia de la distancia media de la ‘heave plate’ a la superficie libre o al fondo del mar, sobre los coeficientes hidrodinámicos. En este proceso, un nuevo modelo que describe el trabajo realizado por la amortiguación en función de la enstrofía, es descrito en el presente documento. Este nuevo enfoque es capaz de proporcionar una correlación directa entre el desprendimiento local de vorticidad y la fuerza de amortiguación global. El análisis también incluye el estudio de los efectos de la geometría de la heave plate, y examina la sensibilidad de los coeficientes hidrodinámicos al incluir porosidad en ésta. Un diseño novedoso de una heave plate, basado en la teoría fractal, también fue analizado experimentalmente y comparado con datos experimentales obtenidos por otros autores. Para la resolución de las ecuaciones de Navier Stokes se ha usado un solver basado en el método de volúmenes finitos. El solver usa las librerías de OpenFOAM (Open source Field Operation And Manipulation), para resolver un problema multifásico e incompresible, usando la técnica VOF (volume of fluid) que permite capturar el movimiento de la superficie libre. Los resultados numéricos han sido comparados con resultados experimentales llevados a cabo en el Canal del Ensayos Hidrodinámicos (CEHINAV) de la Universidad Politécnica de Madrid y en el Canal de Experiencias Hidrodinámicas (CEHIPAR) en Madrid, al igual que con otros experimentos realizados en la Escuela de Ingeniería Mecánica de la Universidad de Western Australia. Los principales resultados se presentan a continuación: 1. Para pequeños valores de KC, los coeficientes hidrodinámicos de masa añadida y amortiguamiento incrementan su valor a medida que el disco se aproxima al fondo marino. Para los casos cuando el disco oscila cerca de la superficie libre, la dependencia de los coeficientes hidrodinámicos es más fuerte por la influencia del movimiento de la superficie libre. 2. Los casos analizados muestran la existencia de un valor crítico de KC, donde la tendencia de los coeficientes hidrodinámicos se ve alterada. Dicho valor crítico depende de la distancia al fondo marino o a la superficie libre. 3. El comportamiento físico del flujo, para valores de KC cercanos a su valor crítico ha sido estudiado mediante el análisis del campo de vorticidad. 4. Introducir porosidad al disco, reduce la masa añadida para los valores de KC estudiados, pero se ha encontrado que la porosidad incrementa el valor del coeficiente de amortiguamiento cuando se incrementa la amplitud del movimiento, logrando un máximo de damping para un disco con 10% de porosidad. 5. Los resultados numéricos y experimentales para los discos con faldón, muestran que usar este tipo de geometrías incrementa la masa añadida cuando se compara con el disco sólido, pero reduce considerablemente el coeficiente de amortiguamiento. 6. Un diseño novedoso de heave plate basado en la teoría fractal ha sido experimentalmente estudiado a diferentes calados y comparado con datos experimentales obtenidos por otro autores. Los resultados muestran un comportamiento incierto de los coeficientes y por tanto este diseño debería ser estudiado más a fondo. ABSTRACT Offshore wind energy is one of the promising resources which can reduce the fossil fuel energy consumption and cover worldwide energy demands. Offshore wind turbine concepts are based on either a fixed structure as a jacket or a floating offshore platform like a semisubmersible, spar or tension leg platform. Floating offshore wind turbines have the potential to be an important part of the energy production profile in the coming years. In order to accomplish this wind integration, these wind turbines need to be made more reliable and cost efficient to be competitive with other sources of energy. Floating offshore artifacts, such oil rings and wind turbines, may experience resonant heave motions in sea states with long peak periods. These heave resonances may increase the system downtime and cause damage on the system components and as well as on risers and mooring systems. The heave resonant response may be reduced by different means: (1) increasing the damping of the system, (2) keeping the natural heave period outside the range of the wave energy, and (3) reducing the heave excitation forces. A typical example to accomplish this reduction are “Heave Plates”. Heave plates are used in the offshore industry due to their hydrodynamic characteristics, i.e., increased added mass and damping. Conventional offshore hydrodynamic analysis considers a structure in waves, and evaluates the linear and nonlinear loads using potential theory. Viscous damping, which is expected to play a crucial role in the resonant response, is an empirical input to the analysis, and is not explicitly calculated. The present research has been mainly focused on the prediction of viscous damping and added mass of floating offshore wind turbine heave plates. In the calculations, the hydrodynamic forces have been measured in order to compute how the hydrodynamic coefficients of added mass1 and damping vary with the KC number, which characterises the amplitude of heave motion relative to the diameter of the disc. In addition, the influence on the hydrodynamic coefficients when the heave plate is oscillating close to the free surface or the seabed has been investigated. In this process, a new model describing the work done by damping in terms of the flow enstrophy, is described herein. This new approach is able to provide a direct correlation between the local vortex shedding processes and the global damping force. The analysis also includes the study of different edges geometry, and examines the sensitivity of the damping and added mass coefficients to the porosity of the plate. A novel porous heave plate based on fractal theory has also been proposed, tested experimentally and compared with experimental data obtained by other authors for plates with similar porosity. A numerical solver of Navier Stokes equations, based on the finite volume technique has been applied. It uses the open-source libraries of OpenFOAM (Open source Field Operation And Manipulation), to solve 2 incompressible, isothermal immiscible fluids using a VOF (volume of fluid) phase-fraction based interface capturing approach, with optional mesh motion and mesh topology changes including adaptive re-meshing. Numerical results have been compared with experiments conducted at Technical University of Madrid (CEHINAV) and CEHIPAR model basins in Madrid and with others performed at School of Mechanical Engineering in The University of Western Australia. A brief summary of main results are presented below: 1. At low KC numbers, a systematic increase in added mass and damping, corresponding to an increase in the seabed proximity, is observed. Specifically, for the cases when the heave plate is oscillating closer to the free surface, the dependence of the hydrodynamic coefficients is strongly influenced by the free surface. 2. As seen in experiments, a critical KC, where the linear trend of the hydrodynamic coefficients with KC is disrupted and that depends on the seabed or free surface distance, has been found. 3. The physical behavior of the flow around the critical KC has been explained through an analysis of the flow vorticity field. 4. The porosity of the heave plates reduces the added mass for the studied porosity at all KC numbers, but the porous heave plates are found to increase the damping coefficient with increasing amplitude of oscillation, achieving a maximum damping coefficient for the heave plate with 10% porosity in the entire KC range. 5. Another concept taken into account in this work has been the heave plates with flaps. Numerical and experimental results show that using discs with flaps will increase added mass when compared to the plain plate but may also significantly reduce damping. 6. A novel heave plate design based on fractal theory has tested experimentally for different submergences and compared with experimental data obtained by other authors for porous plates. Results show an unclear behavior in the coefficients and should be studied further. Future work is necessary in order to address a series of open questions focusing on 3D effects, optimization of the heave plates shapes, etc.

Growth hormone-releasing hormone: An autocrine growth factor for small cell lung carcinoma

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various cancers in vivo. This effect is thought to be exerted through suppression of the pituitary growth hormone–hepatic insulin-like growth factor I (IGF-I) axis and direct inhibition of autocrine/paracrine production of IGF-I and -II in tumors. However, other evidence points to a direct effect of GHRH antagonists on tumor growth that may not implicate IGFs, although an involvement of GHRH in the proliferation of cancer cells has not yet been established. In the present study we investigated whether GHRH can function as an autocrine/paracrine growth factor in small cell lung carcinoma (SCLC). H-69 and H-510A SCLC lines cultured in vitro express mRNA for GHRH, which apparently is translated into peptide GHRH and then secreted by the cells, as shown by the detection of GHRH-like immunoreactivity in conditioned media from the cells cultured in vitro. In addition, the levels of GHRH-like immunoreactivity in serum from nude mice bearing H-69 xenografts were higher than in tumor-free mice. GHRH(1–29)NH2 stimulated the proliferation of H-69 and H-510A SCLCs in vitro, and GHRH antagonist JV-1–36 inhibited it. JV-1–36 administered s.c. into nude mice bearing xenografts of H-69 SCLC reduced significantly (P < 0.05) tumor volume and weight, after 31 days of therapy, as compared with controls. Collectively, our results suggest that GHRH can function as an autocrine growth factor in SCLCs. Treatment with antagonistic analogs of GHRH may offer a new approach to the treatment of SCLC and other cancers.