Experimental and numerical study of SiON microresonators with air and polymer cladding

A systematic experimental and numerical study of the device performance of waveguide-coupled SiON microresonators with air and polymer cladding is presented. Values of device parameters like propagation losses of the microresonator modes, the off-resonance insertion losses, and the straight waveguide to microresonator coupling are determined by applying a detailed fitting procedure to the experimental results and compared to results of detailed numerical simulations. By comparing the propagation losses of the fundamental TE polarized microresonator mode obtained by fitting to the measured spectra to the also experimentally determined propagation losses in the adjacent straight waveguide and the materials losses, it is possible to identify the loss mechanisms in the microresonator. By comparing experimental results for microresonators with air and polymethylmethacrylate cladding and a detailed numerical study, the influence of the cladding index on the bend losses is evaluated. It is demonstrated that the presence of an upper cladding can, under the right conditions, actually be beneficial for loss reduction

On Large Volume Moduli Stabilization in IIB Orientifolds

I present a brief introduction to the construction of explicit type IIB orientifold compactifications and summarize the ‘Large Volume Scenario’ on compact four-modulus Calabi–Yau manifolds. I discuss the relevance of this kind of setups for the physical MSSMlike model building and gravitational cosmology. These notes are based on my talk at the ‘Bogolyubov Kyiv Conference 2009’ on ‘Modern Problems of Theoretical and Mathematical Physics’.Подано короткий вступ до побудови явних компактифiкацiй IIБ орiєнтованих множин та розглянуто “сценарiй великих об’ємiв” для компактних чотиримодульних Калабi–Яу многовидiв. Обговорено доречнiсть таких схем для побудови фiзичної моделi МССМ-типу та для гравiтацiйної космологiї. Основою роботи є доповiдь на “Боголюбовськiй київськiй конференцiї 2009” з “Сучасних проблем теоретичної та математичної фiзики”

The footprint of cometary dust analogs: I. Laboratory experiments of low-velocity impacts and comparison with Rosetta data

Cometary dust provides a unique window on dust growth mechanisms during the onset of planet formation. Measurements by the Rosetta spacecraft show that the dust in the coma of comet 67P/Churyumov-Gerasimenko has a granular structure at size scales from sub-um up to several hundreds of um, indicating hierarchical growth took place across these size scales. However, these dust particles may have been modified during their collection by the spacecraft instruments. Here we present the results of laboratory experiments that simulate the impact of dust on the collection surfaces of COSIMA and MIDAS, instruments onboard the Rosetta spacecraft. We map the size and structure of the footprints left by the dust particles as a function of their initial size (up to several hundred um) and velocity (up to 6 m/s). We find that in most collisions, only part of the dust particle is left on the target; velocity is the main driver of the appearance of these deposits. A boundary between sticking/bouncing and fragmentation as an outcome of the particle-target collision is found at v ~ 2 m/s. For velocities below this value, particles either stick and leave a single deposit on the target plate, or bounce, leaving a shallow footprint of monomers. At velocities > 2 m/s and sizes > 80 um, particles fragment upon collision, transferring up to 50 per cent of their mass in a rubble-pile-like deposit on the target plate. The amount of mass transferred increases with the impact velocity. The morphologies of the deposits are qualitatively similar to those found by the COSIMA instrument.Comment: 14 pages, 12 figures, accepted for publication in MNRA

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

TNF- α augments intratumoural concentrations of doxorubicin in TNF- α -based isolated limb perfusion in rat sarcoma models and enhances anti-tumour effects

We have shown previously that isolated limb perfusion (ILP) in sarcoma-bearing rats results in high response rates when melphalan is used in combination with tumour necrosis factor alpha (TNF-α). This is in line with observations in patients. Here we show that ILP with doxorubicin in combination with TNF-α has comparable effects in two different rat sarcoma tumour models. The addition of TNF-α exhibits a synergistic anti-tumour effect, resulting in regression of the tumour in 54% and 100% of the cases for the BN175-fibrosarcoma and the ROS-1 osteosarcoma respectively. The combination is shown to be mandatory for optimal tumour response. The effect of high dose TNF-α on the activity of cytotoxic agents in ILP is still unclear. We investigated possible modes by which TNF-α could modulate the activity of doxorubicin. In both tumour models increased accumulation of doxorubicin in tumour tissue was found: 3.1-fold in the BN175 and 1.8-fold in the ROS-1 sarcoma after ILP with doxorubicin combined with TNF-α in comparison with an ILP with doxorubicin alone. This increase in local drug concentration may explain the synergistic anti-tumour responses after ILP with the combination. In vitro TNF-α fails to augment drug uptake in tumour cells or to increase cytotoxicity of the drug. These findings make it unlikely that TNF-α directly modulates the activity of doxorubicin in vivo. As TNF-α by itself has no or only minimal effect on tumour growth, an increase in local concentrations of chemotherapeutic drugs might well be the main mechanism for the synergistic anti-tumour effects. © 2000 Cancer Research Campaig

Prediction of fetal and neonatal outcomes after preterm manifestations of placental insufficiency:systematic review of prediction models

Objectives: To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension, pre-eclampsia, HELLP syndrome or fetal growth restriction with its onset before 37 weeks' gestation) and to assess the quality of the models and their performance on external validation. Methods: A systematic literature search was performed in PubMed, Web of Science and EMBASE. Studies describing prediction models for fetal/neonatal mortality or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently. Results: Our literature search yielded 22 491 unique publications. Fourteen were included after full-text screening of 218 articles that remained after initial exclusions. The studies derived a total of 41 prediction models, including four models in the setting of pre-eclampsia or HELLP, two models in the setting of fetal growth restriction and/or pre-eclampsia and 35 models in the setting of fetal growth restriction. None of the models was validated externally, and internal validation was performed in only two studies. The final models contained mainly ultrasound (Doppler) markers as predictors of fetal/neonatal mortality and neonatal morbidity. Discriminative properties were reported for 27/41 models (c-statistic between 0.6 and 0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly owing to the use of inappropriate statistical methods. Conclusions: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered to be of low methodological quality, apart from one that had unclear methodological quality. Higher-quality models and external validation studies are needed to inform clinical decision-making based on prediction models.</p

Optically Thick Radio Cores of Narrow-Waist Bipolar Nebulae

We report our search for optically thick radio cores in sixteen narrow-waist bipolar nebulae. Optically thick cores are a characteristic signature of collimated ionized winds. Eleven northern nebulae were observed with the Very Large Array (VLA) at 1.3 cm and 0.7 cm, and five southern nebulae were observed with the Australia Telescope Compact Array (ATCA) at 6 cm and 3.6 cm. Two northern objects, 19W32 and M 1-91, and three southern objects, He 2-25, He 2-84 and Mz 3, were found to exhibit a compact radio core with a rising spectrum consistent with an ionized jet. Such jets have been seen in M 2-9 and may be responsible for shaping bipolar structure in planetary nebulae.Comment: 29 pages, accepted for publication in Ap

Revealing the mid-infrared emission structure of IRAS 16594-4656 and IRAS 07027-7934

TIMMI2 diffraction-limited mid-infrared images of a multipolar proto-planetary nebula IRAS 16594-4656 and a young [WC] elliptical planetary nebula IRAS 07027-7934 are presented. Their dust shells are for the first time resolved (only marginally in the case of IRAS 07027-7934) by applying the Lucy-Richardson deconvolution algorithm to the data, taken under exceptionally good seeing conditions (<0.5"). IRAS 16594-4656 exhibits a two-peaked morphology at 8.6, 11.5 and 11.7 microns which is mainly attributed to emission from PAHs. Our observations suggest that the central star is surrounded by a toroidal structure observed edge-on with a radius of 0.4" (~640 AU at an assumed distance of 1.6 kpc) with its polar axis at P.A.~80 degrees, coincident with the orientation defined by only one of the bipolar outflows identified in the HST optical images. We suggest that the material expelled from the central source is currently being collimated in this direction and that the multiple outflow formation has not been coeval. IRAS 07027-7934 shows a bright, marginally extended emission (FWHM=0.3") in the mid-infrared with a slightly elongated shape along the N-S direction, consistent with the morphology detected by HST in the near-infrared. The mid-infrared emission is interpreted as the result of the combined contribution of small, highly ionized PAHs and relatively hot dust continuum. We propose that IRAS 07027-7934 may have recently experienced a thermal pulse (likely at the end of the AGB) which has produced a radical change in the chemistry of its central star.Comment: 35 pages, 8 figures (figures 1, 2, 4 and 6 are in low resolution) accepted for publication in Ap

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial)

Background: Syndesmotic injuries are common and their incidence is rising. In case of surgical fixation of the syndesmosis a metal syndesmotic screw is used most often. It is however unclear whether this screw needs to be removed routinely after the syndesmosis has healed. Traditionally the screw is removed after six to 12 weeks as it is thought to hamper ankle functional and to be a source of pain. Some studies however suggest this is only the case in a minority of patients. We therefore aim to investigate the effect of retaining the syndesmotic screw on functional outcome. Design: This is a pragmatic international multicentre randomised controlled trial in patients with an acute syndesmotic injury for which a metallic syndesmotic screw was placed. Patients will be randomised to either routine removal of the syndesmotic screw or removal on demand. Primary outcome is functional recovery at 12 months measured with the Olerud-Molander Score. Secondary outcomes are quality of life, pain and costs. In total 194 patients will be needed to demonstrate non-inferiority between the two interventions at 80% power and a significance level of 0.025 including 15% loss to follow-up. Discussion: If removal on demand of the syndesmotic screw is non-inferior to routine removal in terms of functional outcome, this will offer a strong argument to adopt this as standard practice of care. This means that patients will not have to undergo a secondary procedure, leading to less complications and subsequent lower costs.Peer reviewe