947 research outputs found
The [4+2]âCycloaddition of αâNitrosoalkenes with Thiochalcones as a Prototype of Periselective HeteroâDielsâAlder ReactionsâExperimental and Computational Studies
The [4+2]âcycloadditions of αânitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styrylâsubstituted 4Hâ1,5,2âoxathiazines in moderate to good yields. Of the eight conceivable heteroâDielsâAlder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the αânitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bisâheterocyclic [4+2]âcycloadducts. The experiments are supported by highâlevel DFT calculations that were also extended to related heteroâDielsâAlder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2âdithiin and 2Hâthiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process
The Banathy Conversation Methodology
Context: Thirty years ago, members of the systems science community discovered that at their conferences, more was being accomplished in the breaks than in the sessions. Led by Bela H. Banathy, they cancelled the sessions and created a conversation methodology that has proven far more effective. Dozens of conversations have now been held around the world. Problem: At a recent conversation in Linz, Austria, a team devoted its inquiry to the Banathy Conversation Methodology (BCM) itself, asking, in particular, how to develop and spread the methodology further, beyond the systems science community. Method: The team captured key features and benefits of BCM and developed new tools. Results: Described herein are the development of the methodology, its theoretical underpinnings, the methodology itself, heuristics for successful conversations, and an example of how the methodology is spreading. Implications: Ultimately, the hope is to develop the methodology in such ways that communities could apply it to meet significant challenges and co-create their futures
Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas
Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. Patients and methods: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia â„grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patient
Kinetics of active surface-mediated diffusion in spherically symmetric domains
We present an exact calculation of the mean first-passage time to a target on
the surface of a 2D or 3D spherical domain, for a molecule alternating phases
of surface diffusion on the domain boundary and phases of bulk diffusion. We
generalize the results of [J. Stat. Phys. {\bf 142}, 657 (2011)] and consider a
biased diffusion in a general annulus with an arbitrary number of regularly
spaced targets on a partially reflecting surface. The presented approach is
based on an integral equation which can be solved analytically. Numerically
validated approximation schemes, which provide more tractable expressions of
the mean first-passage time are also proposed. In the framework of this minimal
model of surface-mediated reactions, we show analytically that the mean
reaction time can be minimized as a function of the desorption rate from the
surface.Comment: Published online in J. Stat. Phy
Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations.
Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity
State space modelling and data analysis exercises in LISA Pathfinder
LISA Pathfinder is a mission planned by the European Space Agency to test the
key technologies that will allow the detection of gravitational waves in space.
The instrument on-board, the LISA Technology package, will undergo an
exhaustive campaign of calibrations and noise characterisation campaigns in
order to fully describe the noise model. Data analysis plays an important role
in the mission and for that reason the data analysis team has been developing a
toolbox which contains all the functionalities required during operations. In
this contribution we give an overview of recent activities, focusing on the
improvements in the modelling of the instrument and in the data analysis
campaigns performed both with real and simulated data.Comment: Plenary talk presented at the 9th International LISA Symposium, 21-25
May 2012, Pari
A strategy to characterize the LISA-Pathfinder cold gas thruster system
The cold gas micro-propulsion system that will be used during the LISA-Pathfinder mission will be one of the most important component used to ensure the "free-fall" of the enclosed test masses. In this paper we present a possible strategy to characterize the effective direction and amplitude gain of each of the 6 thrusters of this system
In-flight thermal experiments for LISA pathfinder: simulating temperature noise at the inertial sensors
Thermal Diagnostics experiments to be carried out on board LISA Pathfinder (LPF) will yield a detailed characterisation of how temperature fluctuations affect the LTP (LISA Technology Package) instrument performance, a crucial information for future space based gravitational wave detectors as the proposed eLISA. Amongst them, the study of temperature gradient fluctuations around the test masses of the Inertial Sensors will provide as well information regarding the contribution of the Brownian noise, which is expected to limit the LTP sensitivity at frequencies close to 1 mHz during some LTP experiments. In this paper we report on how these kind of Thermal Diagnostics experiments were simulated in the last LPF Simulation Campaign (November, 2013) involving all the LPF Data Analysis team and using an end-to-end simulator of the whole spacecraft. Such simulation campaign was conducted under the framework of the preparation for LPF operations
Free-flight experiments in LISA Pathfinder
The LISA Pathfinder mission will demonstrate the technology of drag-free test
masses for use as inertial references in future space-based gravitational wave
detectors. To accomplish this, the Pathfinder spacecraft will perform drag-free
flight about a test mass while measuring the acceleration of this primary test
mass relative to a second reference test mass. Because the reference test mass
is contained within the same spacecraft, it is necessary to apply forces on it
to maintain its position and attitude relative to the spacecraft. These forces
are a potential source of acceleration noise in the LISA Pathfinder system that
are not present in the full LISA configuration. While LISA Pathfinder has been
designed to meet it's primary mission requirements in the presence of this
noise, recent estimates suggest that the on-orbit performance may be limited by
this `suspension noise'. The drift-mode or free-flight experiments provide an
opportunity to mitigate this noise source and further characterize the
underlying disturbances that are of interest to the designers of LISA-like
instruments. This article provides a high-level overview of these experiments
and the methods under development to analyze the resulting data.Comment: 13 pages, 5 figures. Accepted to Journal Of Physics, Conference
Series. Presented at 10th International LISA Symposium, May 2014,
Gainesville, FL, US
Seasonal Migration of Sika Deer in the Oku-Chichibu Mountains, Central Japan
Movements and seasonal home ranges of 6 GPS collared sika deer were investigated at the Oku-Chichibu Mountains, central Honshu, from April 2009 to March 2010. All deer migrated between discrete summer and winter home ranges. The linear migration distance ranged from 2.5 to 31.9 km. Mean elevation during the summer and the winter ranged from 980 to 1,782 m, and from 1,204 to 1,723 m, respectively. Two deer were upward migrants and 4 deer were downward migrants. Taking into consideration of the relatively small snow accumulation in the summer home range, the possibility of autumn migration to avoid deep snow is low. The percentage of steep slope in the winter home range was higher than that in the summer. Bamboo grass was not found in the summer home range, but was predominant in the winter home range. Road density decreased in the winter home range compared to the summer. Only 2 out of 6 deer stayed mainly in the wildlife protection area during the winter. Our results indicate that the autumn migration was affected by winter forage and human disturbance, thereby assured the survival of the deer during winter.ArticleMAMMAL STUDY. 37(2):127-137 (2012)journal articl
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