820 research outputs found
Total Synthesis of Iejimalide A-D and Assessment of the Remarkable Actin-Depolymerizing Capacity of These Polyene Macrolides
A concise and convergent total synthesis of the highly cytotoxic marine natural products iejimalide AâD (1â4) is reported, which relies on an effective ring-closing metathesis (RCM) reaction of a cyclization precursor containing no less than 10 double bonds. Because of the exceptional sensitivity of this polyunsaturated intermediate and its immediate precursors toward acid, base, and even gentle warming, the assembly process hinged upon the judicious choice of protecting groups and the careful optimization of all individual transformations. As a consequence, particularly mild protocols for Stille as well as Suzuki reactions of elaborate coupling partners have been developed that hold considerable promise for applications in other complex settings. Moreover, a series of non-natural âiejimalide-likeâ compounds has been prepared, differing from the natural lead in the polar head groups linked to the macrolide's N-terminus. With the aid of these compounds it was possible to uncover the hitherto unknown effect of iejimalide and analogues on the actin cytoskeleton. Their capacity to depolymerize this microfilament network rivals that of the latrunculins which constitute the standard in the field. Structural modifications of the peptidic terminus in 2 are thereby well accommodated, without compromising the biological effects. The iejimalides hence constitute an important new class of probe molecules for chemical biology in addition to their role as promising lead structures for the development of novel anticancer agents
Giant slip lengths of a simple fluid at vibrating solid interfaces
It has been shown recently [PRL 102, 254503 (2009)] that in the plane-plane
configuration a mechanical resonator vibrating close to a rigid wall in a
simple fluid can be overdamped to a frozen regime. Here, by solving
analytically the Navier Stokes equations with partial slip boundary conditions
at the solid fluid interface, we develop a theoretical approach justifying and
extending these earlier findings. We show in particular that in the perfect
slip regime the above mentioned results are, in the plane-plane configuration,
very general and robust with respect to lever geometry considerations. We
compare the results with those obtained previously for the sphere moving
perpendicularly and close to a plane in a simple fluid and discuss in more
details the differences concerning the dependence of the friction forces with
the gap distance separating the moving object (i.e., plane or sphere) from the
fixed plane. Finally, we show that the submicron fluidic effect reported in the
reference above, and discussed further in the present work, can have dramatic
implications in the design of nano-electromechanical systems (NEMS).Comment: submitted to PRE (see also PRL 102, 254503 (2009)
Anisotropy and controllable band structure in supra-wavelength polaritonic metasurfaces
In this letter we exploit the extended coherence length of mixed
plasmon/exciton states to generate active metasurfaces. For this purpose,
periodic stripes of organic dye are deposited on a continuous silver film.
Typical metasurface effects, such as effective behavior and geometry
sensitivity, are measured for periods exceeding the polaritonic wavelength by
more than one order of magnitude. By adjusting the metasurface geometry,
anisotropy, modified band structure and unidimensional polaritons are
computationally simulated and experimentally observed in reflectometry as well
as in emission.Comment: 4 figures, 1 Supplementary Material
Unveiling the intruder deformed 0 state in Si
The 0 state in Si has been populated at the {\sc Ganil/Lise3}
facility through the -decay of a newly discovered 1 isomer in
Al of 26(1) ms half-life. The simultaneous detection of pairs
allowed the determination of the excitation energy E(0)=2719(3) keV and
the half-life T=19.4(7) ns, from which an electric monopole strength of
(E0)=13.0(0.9) was deduced. The 2 state is
observed to decay both to the 0 ground state and to the newly observed
0 state (via a 607(2) keV transition) with a ratio
R(2)=1380(717). Gathering all
information, a weak mixing with the 0 and a large deformation parameter
of =0.29(4) are found for the 0 state, in good agreement with
shell model calculations using a new {\sc sdpf-u-mix} interaction allowing
\textit{np-nh} excitations across the N=20 shell gap.Comment: 5 pages, 3 figures, accepted for publication in Physical Review
Letter
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Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR)*
Summary Background: Psoriasis is associated with several comorbidities and behavioural risk factors. Objectives: To evaluate demographic and disease characteristics in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: PSOLAR is a global, prospective, longitudinal, disease-based registry that includes a postmarketing commitment to evaluate safety in patients with psoriasis. Enrolled patients had to be receiving, or be eligible to receive, conventional systemic or biological agents. Demographic/disease characteristics, medical histories, lifestyle risk factors and previous treatments are collected at enrolment. Efficacy and safety data are collected every 6 months for 8 years, and data are extracted annually. Selected parameters are evaluated by age quartile using post hoc analyses. Results: As of 23 August 2012, 11 900 patients were enrolled at 301 sites in North America, Europe and Latin America. Over half of the PSOLAR population (54·7%) is male, with a mean age of 48·6 years and mean body mass index of 30·9 kg mâ2 at enrolment. Mean duration of disease at enrolment was 17·5 years, and mean Physician's Global Assessment score was 2·0. Psoriatic arthritis (35·5%) and cardiovascular diseases (38·2%) were highly prevalent. Diabetes mellitus type II was reported in 11·4% of patients. Depression and anxiety were noted in 14·7% and 11·1% of patients, respectively; 79·0% reported any alcohol use and 56·7% reported smoking or a history of smoking. The occurrence of most comorbidities, including cardiovascular disease and risk factors, increased with age. Conclusions: In the PSOLAR population, multiple and age-appropriate comorbidities are associated with psoriasis and may affect the selection of psoriasis treatments. What's already known about this topic? Psoriasis is a complicated disorder, often accompanied by multiple comorbidities. Demographic and disease characteristics of patients with psoriasis reported from large claims datasets may be affected by misclassification bias or coding errors. In clinical trials, many patients are excluded owing to strict inclusion criteria. What does this study add? Data collected by the Psoriasis Longitudinal Assessment and Registry reveal that the demographics and disease characteristics of patients with psoriasis who are receiving, or are candidates for, systemic therapy in actual clinical care resemble those reported in clinical trials. Most comorbidities occur more frequently in older patients, who, in turn, may require more comprehensive overall medical care
Studies on Iejimalide B: Preparation of the Seco Acid and Identification of the Molecule's "Achilles Heel"
Limitations of models in total synthesis are illustrated by a study towards the potent cytotoxic macrolide iejimalide B. Although the Yamaguchi protocol allowed for the esterification of elaborate segments, attempted macrolactonization of the seco acid met with failure (see scheme, Boc= tert-butyloxycarbonyl). The assembly of the seco acid involves some of the most advanced applications of the Julia olefination known to date
Sub-surface Oxygen and Surface Oxide Formation at Ag(111): A Density-functional Theory Investigation
To help provide insight into the remarkable catalytic behavior of the
oxygen/silver system for heterogeneous oxidation reactions, purely sub-surface
oxygen, and structures involving both on-surface and sub-surface oxygen, as
well as oxide-like structures at the Ag(111) surface have been studied for a
wide range of coverages and adsorption sites using density-functional theory.
Adsorption on the surface in fcc sites is energetically favorable for low
coverages, while for higher coverage a thin surface-oxide structure is
energetically favorable. This structure has been proposed to correspond to the
experimentally observed (4x4) phase. With increasing O concentrations, thicker
oxide-like structures resembling compressed Ag2O(111) surfaces are
energetically favored. Due to the relatively low thermal stability of these
structures, and the very low sticking probability of O2 at Ag(111), their
formation and observation may require the use of atomic oxygen (or ozone, O3)
and low temperatures. We also investigate diffusion of O into the sub-surface
region at low coverage (0.11 ML), and the effect of surface Ag vacancies in the
adsorption of atomic oxygen and ozone-like species. The present studies,
together with our earlier investigations of on-surface and
surface-substitutional adsorption, provide a comprehensive picture of the
behavior and chemical nature of the interaction of oxygen and Ag(111), as well
as of the initial stages of oxide formation.Comment: 17 pages including 14 figures, Related publications can be found at
http://www.fhi-berlin.mpg.de/th/paper.htm
Dynamique des ongulés sauvages dans la région méditerranéenne française
La politique de restauration des populations dâongulĂ©s, entreprise Ă partir des annĂ©es 70, a montrĂ© son efficacitĂ© aussi bien au niveau national quâen rĂ©gion mĂ©diterranĂ©enne, oĂč tous les ongulĂ©s sont en expansion : le sanglier, le chevreuil, le cerf, le mouflon et mĂȘme le chamois qui descend des montagnes pour coloniser les forĂȘts de chĂȘne vert. Toutefois, les mĂ©thodes de comptage appliquĂ©es depuis plusieurs dĂ©cennies ne permettent plus une gestion efficace des ongulĂ©s sauvages car elles sous-estiment systĂ©matiquement les effectifs et ne font quâaggraver le phĂ©nomĂšne dâexplosion des populations. Le rĂ©sultat en est une dĂ©gradation de la qualitĂ© des animaux et lâapparition de dĂ©gĂąts sur la vĂ©gĂ©tation. Ainsi, depuis quelques annĂ©es, une nouvelle approche de gestion durable commence Ă ĂȘtre appliquĂ©e par certains gestionnaires. Cette gestion, basĂ©e sur les indicateurs de changement Ă©cologique (ICE), cherche Ă Ă©valuer lâinteraction entre les ongulĂ©s sauvages et le milieu pour maintenir un Ă©quilibre entre les niveaux de populations et les ressources alimentaires
A database of aircraft measurements of carbon monoxide (CO) with high temporal and spatial resolution during 2011â2021
To understand tropospheric air pollution at regional and global scales, the
SPIRIT (SPectromĂštre Infra-Rouge In situ Toute
altitude) airborne instrument was developed and used on aircraft to measure volume mixing ratios
of carbon monoxide (CO), an important indicator of air pollution, during the
last decade. SPIRIT provides high-quality CO measurements with 1Ï precision of 0.3âppbv at a time resolution of 1.6âs thanks to the coupling
of a quantum cascade laser to a Robert optical multi-pass cell. It can be
operated on different aircraft such as Falcon-20 and ATR-42 from the German Aerospace Agency (DLR)
and from SAFIRE (CNRS-CNES-Météo France). With support from
various projects, measurements were taken for more than 200 flight hours
over three continents (Europe, Asia, and Africa), including two
intercontinental transects (EuropeâAsia and EuropeâAfrica). Levels of CO
and its spatial distribution are briefly discussed and compared between
different regions/continents. CO generally decreases with altitude except in
some cases, indicating the important contribution of long-distance transport
to CO levels. A 3D trajectory mapped by CO level was plotted for each flight
and is presented in this study (which includes a Supplement). The
database is archived in the AERIS database (https://doi.org/10.25326/440), the French national center for atmospheric
observations (Catoire et al., 2023). In addition, it could help
to validate model performance and satellite measurements. For instance, the
database covers measurements at high-latitude regions (i.e., Kiruna, Sweden,
68ââN), where satellite measurements are still challenging, and at
low-latitude regions (West Africa and Southeast Asia), where in situ data
are scarce and satellites need more validation by airborne measurements.</p
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