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For almost 160 years, it has been known that Helmholtz oscillations, unique to vibrating strings in bowed instruments (violin, cello, etc.), have two distinct regimes: "slip" and "stick." During the slip regime, the force at the bow-string interaction is attributed to friction between the sliding bow hair and the vibrating string, with a friction coefficient that decreases with increasing relative velocity. Yet the hair-string interaction during the stick regime is less understood. We propose that the interaction force during the stick regime is proportional to the product of the longitudinal acoustic impedance of the bow hair to the relative bow-string velocity. We validate this hypothesis by solving the string's differential equation of motion, including an enhanced formulation to avoid parasitic high-frequency oscillations. This physical model enables us to analyze, in real time, the characteristics of the Helmholtz oscillations, including the string shape, excitation of harmonics, Schelleng ripples, and string energy, showing that the bowed string gains energy during the stick regime and loses energy during the slip regime.
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BACKGROUND: Children and adolescents with severe hemophilia commonly suffer from acute and chronic pain as a consequence of hemophilia-related bleeding. Intervention-related pain also plays a major role. Despite its high prevalence in this patient group, hemophilia-related pain is not always adequately addressed and sufficiently treated. OBJECTIVES: This paper discusses how to improve pain management for children and adolescents (0-18 years) with hemophilia and which specific features in this population should influence decisions in pain management. MATERIALS AND METHODS: An expert panel discussed challenges in pain treatment in children and adolescents with hemophilia. Recommendations are based on evidence and clinical experience. RESULT: Pain management in children with hemophilia needs improvement. Children with hemophilia are at risk of developing chronic pain and of suffering traumatization due to insufficient pain management. Pain therapy can be challenging in these children as both their age and the underlying disease limit the options in particular in pain medication. The expert panel developed recommendations to improve pain management in children with hemophilia.
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Dolor Crónico , Hemofilia A , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Manejo del DolorRESUMEN
The goal of this randomized and controlled study was to examine whether whole-body vibration (WBV) training is able to reduce back pain and physical disability in seated working office employees with chronic low-back pain in a real-world setting. A total of 41 subjects (68.3% female/mean age 45.5±9.1 years/mean BMI 26.6±5.2) were randomly allocated to an intervention group (INT [n=21]) or a control group (CON [n=20]). The INT participated in WBV training 2.5 times per week for 3 months. The primary outcome was the change in the Roland and Morris disability questionnaire (RMQ) score over the study period. In addition, secondary outcomes included changes in the Oswestry Disability Index (ODI), the Work Ability Index Questionnaire, the quality of life questionnaire SF-36, the Freiburger activity questionnaire, and an isokinetic test of the musculature of the trunk. Compliance with the intervention in the INT reached a mean of 81.1%±31.2% with no long-lasting unwanted side effects. We found significant positive effects of 3 months of WBV training in the INT compared to the CON regarding the RMQ (P=.027), the ODI (P=.002), the SF-36 (P=.013), the Freiburger activity questionnaire (P=.022), the post-interventional sick-leave in the INT (P=.008), and trends regarding a positive effect of the intervention on the muscular capacity of the muscles of the trunk in flexion. WBV training seems to be an effective, safe, and suitable intervention for seated working employees with chronic low-back pain.
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Dolor de la Región Lumbar/terapia , Modalidades de Fisioterapia , Vibración , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiología , Salud Laboral , Postura , Calidad de Vida , Rango del Movimiento Articular , Ausencia por Enfermedad , Encuestas y Cuestionarios , Torso , Lugar de TrabajoRESUMEN
We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross-spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed ΛCDM is detected at modest significance in the 95×150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23×95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23×353. We take the likelihood of all the spectra for a multicomponent model including lensed ΛCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves.
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BACKGROUND: Population-based data on pediatric patients on long-term respiratory support (LTRS) in Austria are lacking. This study aimed to record the pediatric departments active in this field, as well as number and characteristics of patients on LTRS. METHODS: A national cross-sectional study was carried out by means of questionnaires sent to all pediatric departments in Austria. RESULTS: All departments answered to the questionnaires. On June 1st, 2013, the reference day for this study, 12 of the 41 pediatric departments in Austria were active in the field. At this time, these centers were caring for 143 patients, 111 (77.6%) of them under 18 years, which corresponds to a prevalence of 7.4 per 100 000. The patients suffered from neuromuscular disorders (44%), other neurological disorders (18.9%), disorders of respiratory drive (9.1%), obstructive sleep apnea (8.4%), thoracal and spinal diseases (8.4%), pulmonary disorders (4.9%) and other diseases (6.3%). Continuous positive airway pressure was used in 6.3%, non-invasive ventilation in 60.1% and invasive ventilation in 33.6% of the patients, respectively. LTRS was performed at home in 92.3%. CONCLUSION: LTRS represents a common management strategy in children and adolescents with a variety of disorders. Census reports such as this one provide the basis for appropriate planning of resource allocation. The age distribution of our patients shows the need for structured transition into adult care.
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Cuidados a Largo Plazo/métodos , Cuidados a Largo Plazo/tendencias , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/terapia , Adolescente , Austria , Niño , Preescolar , Enfermedad Crónica , Estudios Transversales , Femenino , Servicios de Atención a Domicilio Provisto por Hospital/estadística & datos numéricos , Servicios de Atención a Domicilio Provisto por Hospital/tendencias , Humanos , Recién Nacido , Cuidados a Largo Plazo/estadística & datos numéricos , Masculino , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Encuestas y Cuestionarios , Revisión de Utilización de Recursos/estadística & datos numéricosRESUMEN
BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Neoplasias Óseas/cirugía , Niño , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Terapia Neoadyuvante , Osteosarcoma/cirugía , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Calidad de Vida , Proyectos de Investigación , Adulto JovenRESUMEN
INTRODUCTION: Disturbances of circadian rhythms occur in all episodes of bipolar disorder (BD). Lithium, as gold-standard in the maintenance treatment of BD, is known to influence circadian processes. METHODS: In a pilot study lymphoblastoid cell lines (LCLs) were generated from 8 BD patients and 6 healthy controls. The LCLs were treated with lithiumchloride (LiCl) for 3 weeks. Cell cycles were then synchronized and expressional analysis by quantitative Real Time PCR was done. RESULTS: BD and controls differed in the period length regarding DBP (albumin D-box binding protein) expression and DBP expression was also influenced by lithium treatment. Furthermore, baseline DBP expression was significantly different between non-treated BD and healthy controls. None of the other analyzed circadian genes showed to be influenced by chronic lithium treatment or to be differentially regulated due to the diagnosis. DISCUSSION: We here show that chronic lithium treatment of LCLs leads to decreased expression of the clock gene DBP, rendering DBP a lithium-regulated gene. We could confirm the role of the circadian clock as well in lithium mode of action as in the pathomechanisms of BD although future studies with a greater number of participants and cell lines are needed.
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Antimaníacos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Relojes Circadianos , Proteínas de Unión al ADN/biosíntesis , Expresión Génica/efectos de los fármacos , Cloruro de Litio/farmacología , Factores de Transcripción/biosíntesis , Línea Celular , Femenino , Humanos , Masculino , Proyectos PilotoRESUMEN
We report results from the BICEP2 experiment, a cosmic microwave background (CMB) polarimeter specifically designed to search for the signal of inflationary gravitational waves in the B-mode power spectrum around ââ¼80. The telescope comprised a 26 cm aperture all-cold refracting optical system equipped with a focal plane of 512 antenna coupled transition edge sensor 150 GHz bolometers each with temperature sensitivity of ≈300 µK(CMB)âs. BICEP2 observed from the South Pole for three seasons from 2010 to 2012. A low-foreground region of sky with an effective area of 380 square deg was observed to a depth of 87 nK deg in Stokes Q and U. In this paper we describe the observations, data reduction, maps, simulations, and results. We find an excess of B-mode power over the base lensed-ΛCDM expectation in the range 30 < â < 150, inconsistent with the null hypothesis at a significance of >5σ. Through jackknife tests and simulations based on detailed calibration measurements we show that systematic contamination is much smaller than the observed excess. Cross correlating against WMAP 23 GHz maps we find that Galactic synchrotron makes a negligible contribution to the observed signal. We also examine a number of available models of polarized dust emission and find that at their default parameter values they predict power â¼(5-10)× smaller than the observed excess signal (with no significant cross-correlation with our maps). However, these models are not sufficiently constrained by external public data to exclude the possibility of dust emission bright enough to explain the entire excess signal. Cross correlating BICEP2 against 100 GHz maps from the BICEP1 experiment, the excess signal is confirmed with 3σ significance and its spectral index is found to be consistent with that of the CMB, disfavoring dust at 1.7σ. The observed B-mode power spectrum is well fit by a lensed-ΛCDM+tensor theoretical model with tensor-to-scalar ratio r = 0.20_(-0.05)(+0.07), with r = 0 disfavored at 7.0σ. Accounting for the contribution of foreground, dust will shift this value downward by an amount which will be better constrained with upcoming data sets.
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BACKGROUND: The aim of this multicenter study was to establish a diagnostic algorithm using molecular methods for the diagnosis of C. difficile-associated infection (CDI). In addition patient specific data were taken into consideration for the interpretation of the results. METHODS: We compared the performance of six different commercially available PCR-tests, two toxin immunoassays, and a glutamat-dehydrogenase test by analysing liquid stool specimens from patients with suspected CDI. Toxigenic culture on CLO-agar was used as reference method. RESULTS: In total 250 stool specimens were collected at two study sites. 77 (30.8%) stool samples were culture-positive for toxigenic C. difficile. 173 (69.2%) specimens showed no growth of C. difficile. As a result, each of the PCR assays tested for C. difficile had a significantly higher sensitivity (94.8% - 100%) and NPV (97.6% - 100%) than the TOX-EIA with a sensitivity of 57.1% and NPV of 83.8%. Specificity of the PCR tests was 94.1% to 96.0% and PPV between 86.5% and 91.6%. The analysis of the patient data revealed a significant difference (p-value 0.0202) between toxin-positive and toxin-negative patients regarding prior antibiotic treatment, especially for cephalosporins. CONCLUSIONS: Our findings support the recommendation to restrict the use of antibiotics as a cornerstone in the prevention of CDI. We conclude that all of the PCR assays evaluated in this study can be applied in a diagnostic algorithm.
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Clostridioides difficile/metabolismo , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/microbiología , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Niño , Preescolar , Infecciones por Clostridium/genética , Heces , Femenino , Glutamato Deshidrogenasa/análisis , Humanos , Técnicas para Inmunoenzimas/métodos , Lactante , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Cantharidin and sodium fluoride inhibit the activity of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) and increase the force of contraction in human atrial preparations. R-phenylisopropyl adenosine (R-PIA) acts as an agonist at A1-adenosine receptors. R-PIA exerts a negative inotropic effect on human atria. The effect of R-PIA-and its various manifestations-are currently explained as a function of the inhibition of sarcolemmal adenylyl cyclase activity and/or opening of sarcolemmal potassium channels. We hypothesise that cantharidin and sodium fluoride may attenuate the negative inotropic effect of R-PIA. During open heart surgery, trabeculae carneae from the right atrium were obtained for human atrial preparations (HAPs). These trabeculae were mounted in organ baths and electrically stimulated at 1 Hz. Furthermore, we studied isolated electrically stimulated left atrial (LA) preparations from female wild-type mice (CD1). The force of contraction was recorded under isometric conditions. R-PIA (1 µM) exerted a rapid negative inotropic effect in the HAPs and mice LA preparations. These negative inotropic effects of R-PIA were attenuated by pre-incubation for 30 min with 100-µM cantharidin in HAPs, but not in mice LA preparations. Adenosine signals via A1 receptors in a species-specific pathway in mammalian atria. We postulate that R-PIA, at least in part, exerts a negative inotropic effect via activation of serine/threonine phosphatases in the human atrium.
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We present a novel achromatic, planar, periodic mirror structure for single-beam magneto-optical trapping and demonstrate its use in the first- and second-stage cooling and trapping for different isotopes of strontium. We refer to it as a Fresnel magneto-optical trap (MOT) as the structure is inspired by Fresnel lenses. By design, it avoids many of the problems that arise for multi-color cooling using planar structures based on diffraction gratings, which have been the dominant planar structures to be used for single-beam trapping thus far. In addition to a complex design process and cost-intensive fabrication, diffraction gratings suffer from their inherent chromaticity, which causes different axial displacements of trap volumes for different wavelengths and necessitates trade-offs in their diffraction properties and achievable trap depths. In contrast, the Fresnel-reflector structure presented here is a versatile, easy-to-manufacture device that combines achromatic beam steering with the advantages of a planar architecture. It enables miniaturizing trapping systems for alkaline-earth-like atoms with multiple cooling transitions as well as multi-species trapping in the ideal tetrahedral configuration and within the same volume above the structure. Our design presents a novel approach for the miniaturization of cold-atom systems based on single-beam MOTs and enables the widespread adoption of these systems.
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At present, the best optical lattice clocks are based on the spectroscopy of trapped alkaline-earth-like atoms such as ytterbium and strontium. The development of mobile or even space-borne clocks necessitates concepts for the compact laser-cooling and trapping of these atoms with reduced laser requirements. Here, we present two compact and robust achromatic mirror structures for single-beam magneto-optical trapping of alkaline-earth-like atoms using two widely separated optical cooling frequencies. We have compared the trapping and cooling performance of a monolithic aluminum structure that generates a conventional trap geometry to a quasi-planar platform based on a periodic mirror structure for different isotopes of Yb. Compared to prior work with strontium in non-conventional traps, where only bosons were trapped on a narrow line transition, we demonstrate two-stage cooling and trapping of a fermionic alkaline-earth-like isotope in a single-beam quasi-planar structure.
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BACKGROUND: The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine. PATIENTS AND METHODS: Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome. RESULTS: The median age was 29 years (range 5-58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1-22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05). CONCLUSIONS: Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcomas.
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Osteosarcoma , Columna Vertebral/patología , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/radioterapia , Osteosarcoma/cirugía , Dolor , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Elderly people are more susceptible to pneumococcal infections. Data in Germany from 2005-2010 shows that especially seniors are prone to develop serious complications such as sepsis. Women are obviously less affected than men. Most of the infections occurred during the winter months. The majority of isolates, i.e., about 80%, possess capsular polysaccharide antigens which are represented in the 23-valent vaccine. Consequently, it could be assumed that the severe complications ensuing long hospital stays and associated with a high mortality could have been avoided, if the elderly people would have been vaccinated, which, however, was only true in a small proportion (28%). Recently, a new conjugated vaccine was introduced to the market. In principle, several antibiotics are available for direct antibacterial treatment. All isolates are susceptible to cefotaxime as well as to ceftriaxone. Resistance to penicillin as well as ampicillin is very rare in Germany. The vast majority of isolates are susceptible to quinolones such as levofloxacin and moxifloxacin. Resistance to macrolides, for example to erythromycin, occurs to a certain extent but the percentage has been declining in recent years. Nevertheless, in many instances therapy is too late. Thus, prevention is of great importance.
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Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Vacunación/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Factores de Riesgo , Resultado del TratamientoRESUMEN
Cantharidin, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), is known to increase the force of contraction and shorten the time to relaxation in human ventricular preparations. We hypothesized that cantharidin has similar positive inotropic effects in human right atrial appendage (RAA) preparations. RAA were obtained during bypass surgery performed on human patients. These trabeculae were mounted in organ baths and electrically stimulated at 1 Hz. For comparison, we studied isolated electrically stimulated left atrial (LA) preparations and isolated spontaneously beating right atrial (RA) preparations from wild-type mice. Cumulatively applied (starting at 10 to 30 µM), cantharidin exerted a positive concentration-dependent inotropic effect that plateaued at 300 µM in the RAA, LA, and RA preparations. This positive inotropic effect was accompanied by a shortening of the time to relaxation in human atrial preparations (HAPs). Notably, cantharidin did not alter the beating rate in the RA preparations. Furthermore, cantharidin (100 µM) increased the phosphorylation state of phospholamban and the inhibitory subunit of troponin I in RAA preparations, which may account for the faster relaxation observed. The generated data indicate that PP1 and/or PP2A play a functional role in human atrial contractility.
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Fibrilación Atrial , Cantaridina , Humanos , Ratones , Animales , Cantaridina/farmacología , Fosforilación , Contracción Miocárdica , Atrios CardíacosRESUMEN
Ultrastable lasers are essential tools in optical frequency metrology enabling unprecedented measurement precision that impacts on fields such as atomic timekeeping, tests of fundamental physics, and geodesy. To characterise an ultrastable laser it needs to be compared with a laser of similar performance, but a suitable system may not be available locally. Here, we report a comparison of two geographically separated lasers, over the longest ever reported metrological optical fibre link network, measuring 2220 km in length, at a state-of-the-art fractional-frequency instability of 7 × 10-17 for averaging times between 30 s and 200 s. The measurements also allow the short-term instability of the complete optical fibre link network to be directly observed without using a loop-back fibre. Based on the characterisation of the noise in the lasers and optical fibre link network over different timescales, we investigate the potential for disseminating ultrastable light to improve the performance of remote optical clocks.
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We discuss the evolution of the atmosphere of early Earth and of terrestrial exoplanets which may be capable of sustaining liquid water oceans and continents where life may originate. The formation age of a terrestrial planet, its mass and size, as well as the lifetime in the EUV-saturated early phase of its host star play a significant role in its atmosphere evolution. We show that planets even in orbits within the habitable zone of their host stars might not lose nebular- or catastrophically outgassed initial protoatmospheres completely and could end up as water worlds with CO2 and hydrogen- or oxygen-rich upper atmospheres. If an atmosphere of a terrestrial planet evolves to an N2-rich atmosphere too early in its lifetime, the atmosphere may be lost. We show that the initial conditions set up by the formation of a terrestrial planet and by the evolution of the host star's EUV and plasma environment are very important factors owing to which a planet may evolve to a habitable world. Finally we present a method for studying the discussed atmosphere evolution hypotheses by future UV transit observations of terrestrial exoplanets.
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Atmósfera/química , Evolución Planetaria , Hidrógeno/química , Rayos Ultravioleta , Dióxido de Carbono/química , Estrellas Celestiales , VaporRESUMEN
Sphingolipids are key components of eukaryotic plasma membranes that are involved in many functions, including the formation signal transduction complexes. In addition, these lipid species and their catabolites function as secondary signalling molecules in, amongst other processes, apoptosis. The biosynthetic pathway for the formation of sphingolipid is largely conserved. However, unlike mammalian cells, fungi, protozoa and plants synthesize inositol phosphorylceramide (IPC) as their primary phosphosphingolipid. This key step involves the transfer of the phosphorylinositol group from phosphatidylinositol (PI) to phytoceramide, a process catalysed by IPC synthase in plants and fungi. This enzyme activity is at least partly encoded by the AUR1 gene in the fungi, and recently the distantly related functional orthologue of this gene has been identified in the model plant Arabidopsis. Here we functionally analysed all three predicted Arabidopsis IPC synthases, confirming them as aureobasidin A resistant AUR1p orthologues. Expression profiling revealed that the genes encoding these orthologues are differentially expressed in various tissue types isolated from Arabidopsis.
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Arabidopsis/enzimología , Arabidopsis/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Hexosiltransferasas/genética , Arabidopsis/efectos de los fármacos , Depsipéptidos/farmacología , Resistencia a Medicamentos/efectos de los fármacos , Etiquetas de Secuencia Expresada , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Prueba de Complementación Genética , Hexosiltransferasas/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Mutación/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismoRESUMEN
Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.
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Apoptosis , Citocinas , Endotelio Vascular/fisiología , Inhibidores de Crecimiento/fisiología , Proteínas de Neoplasias/fisiología , Proteínas de Unión al ARN/fisiología , Células Tumorales Cultivadas/patología , Animales , Apoptosis/efectos de los fármacos , Carcinoma Pulmonar de Lewis , Bovinos , División Celular/efectos de los fármacos , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/farmacología , Inhibidores de Crecimiento/sangre , Inhibidores de Crecimiento/genética , Inhibidores de Crecimiento/farmacocinética , Humanos , Infusiones Intravenosas , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/farmacocinética , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/genética , Proteínas de Unión al ARN/sangre , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/farmacocinética , Proteínas Recombinantes/sangre , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacología , Distribución Tisular/genética , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Zinc oxide (ZnO) thin films were grown on uncoated and zinc-coated Corning glass substrates by pulsed-laser deposition (PLD). X-ray diffraction measurements revealed that the as-deposited films are polycrystalline having preferential orientation along the [0002] and [[Formula: see text]] directions. Transmittance spectroscopy verified that the as-deposited films are transparent with a direct bandgap of about 3.28 eV at room temperature. Piezoresponse imaging and local hysteresis loop acquisition were performed to characterize the piezoelectric and possible ferroelectric properties of the films. The out-of-plane (effective longitudinal, d(parellel)) and in-plane (effective shear, d(perpendicular)) coefficients were estimated from the local piezoresponse based on the comparison with LiNbO(3) single crystals. Measurements of all three components of piezoresponse (one longitudinal and two shear signals) allowed constructing piezoelectric maps for polycrystalline ZnO and to relate the variation of piezoelectric properties to the crystallographic and grain structure of the films. A shifted piezoresponse hysteresis loop under high voltages hints at the possible pseudoferroelectricity, as discussed recently by Tagantsev (2008 Appl. Phys. Lett. 93 202905).