274 research outputs found
Total Syntheses of Amphidinolide H and G
Eureka! The first conquest of the exceptionally potent cytotoxic agent amphidinolideâ
H, which exhibits activity in the picomolar range against human epidermoid cancer cells, was long overdue. The successful route critically hinges upon the scrupulous optimization of the fragment-coupling events (see picture; RCM=ring-closing metathesis) and on the careful adjustment of the peripheral protecting-group pattern
Total Syntheses of Amphidinolides B1, B4, G1, H1 and Structure Revision of Amphidinolide H2
Nature is a pretty unselective âchemistâ when it comes to making the highly cytotoxic amphidinolide macrolides of the B/G/H series. To date, 16 different such compounds have been isolated, all of which could now be approached by a highly convergent and largely catalysis-based route (see figure). This notion is exemplified by the total synthesis of five prototype members of this family. Dinoflagellates of the genus Amphidinium produce a âlibraryâ of closely related secondary metabolites of mixed polyketide origin, which are extremely scarce but highly promising owing to the exceptional cytotoxicity against various cancer cell lines. Because of the dense array of sensitive functionalities on their largely conserved macrocyclic frame, however, these amphidinolides of the B, D, G and H types elapsed many previous attempts at their synthesis. Described herein is a robust, convergent and hence general blueprint which allowed not only to conquest five prototype members of these series, but also holds the promise of making ânon-naturalâ analogues available by diverted total synthesis. This notion transpires for a synthesis-driven structure revision of amphidinolide H2. The successful route hinges upon a highly productive StilleâMigita cross-coupling reaction at the congested and chemically labile 1,3-diene site present in all such targets, which required the development of a modified chloride- and fluoride-free protocol. The macrocyclic ring could be formed with high efficiency and selectivity by ring-closing metathesis (RCM) engaging a vinyl epoxide unit as one of the reaction partners. Because of the sensitivity of the targets to oxidizing and reducing conditions as well as to pH changes, the proper adjustment of the protecting group pattern for the peripheral -OH functions also constitutes a critical aspect, which has to converge to silyl groups only once the diene is in place. Tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF) turned out to be a sufficiently mild fluoride source to allow for the final deprotection without damaging the precious macrolides
The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax
CARIOQA: Definition of a Quantum Pathfinder Mission
A strong potential gain for space applications is expected from the
anticipated performances of inertial sensors based on cold atom interferometry
(CAI) that measure the acceleration of freely falling independent atoms by
manipulating them with laser light. In this context, CNES and its partners
initiated a phase 0 study, called CARIOQA, in order to develop a Quantum
Pathfinder Mission unlocking key features of atom interferometry for space and
paving the way for future ambitious space missions utilizing this technology.
As a cornerstone for the implementation of quantum sensors in space, the
CARIOQA phase 0 aimed at defining the Quantum Pathfinder Mission's scenario and
associated performance objectives. To comply with these objectives, the payload
architecture has been designed to achieve long interrogation time and active
rotation compensation on a BEC-based atom interferometer. A study of the
satellite architecture, including all the subsystems, has been conducted.
Several technical solutions for propulsion and attitude control have been
investigated in order to guarantee optimal operating conditions (limitation of
micro-vibrations, maximization of measurement time). A preliminary design of
the satellite platform was performed.Comment: Proceedings of International Conference on Space Optics (ICSO) 2022;
3-7 October 2022; Dubrovnik; Croati
Tunneling control and localization for Bose-Einstein condensates in a frequency modulated optical lattice
The similarity between matter waves in periodic potential and solid-state
physics processes has triggered the interest in quantum simulation using
Bose-Fermi ultracold gases in optical lattices. The present work evidences the
similarity between electrons moving under the application of oscillating
electromagnetic fields and matter waves experiencing an optical lattice
modulated by a frequency difference, equivalent to a spatially shaken periodic
potential. We demonstrate that the tunneling properties of a Bose-Einstein
condensate in shaken periodic potentials can be precisely controlled. We take
additional crucial steps towards future applications of this method by proving
that the strong shaking of the optical lattice preserves the coherence of the
matter wavefunction and that the shaking parameters can be changed
adiabatically, even in the presence of interactions. We induce reversibly the
quantum phase transition to the Mott insulator in a driven periodic potential.Comment: Laser Physics (in press
Complex lithium ion dynamics in simulated LiPO3 glass studied by means of multi-time correlation functions
Molecular dynamics simulations are performed to study the lithium jumps in
LiPO3 glass. In particular, we calculate higher-order correlation functions
that probe the positions of single lithium ions at several times. Three-time
correlation functions show that the non-exponential relaxation of the lithium
ions results from both correlated back-and-forth jumps and the existence of
dynamical heterogeneities, i.e., the presence of a broad distribution of jump
rates. A quantitative analysis yields that the contribution of the dynamical
heterogeneities to the non-exponential depopulation of the lithium sites
increases upon cooling. Further, correlated back-and-forth jumps between
neighboring sites are observed for the fast ions of the distribution, but not
for the slow ions and, hence, the back-jump probability depends on the
dynamical state. Four-time correlation functions indicate that an exchange
between fast and slow ions takes place on the timescale of the jumps
themselves, i.e., the dynamical heterogeneities are short-lived. Hence, sites
featuring fast and slow lithium dynamics, respectively, are intimately mixed.
In addition, a backward correlation beyond the first neighbor shell for highly
mobile ions and the presence of long-range dynamical heterogeneities suggest
that fast ion migration occurs along preferential pathways in the glassy
matrix. In the melt, we find no evidence for correlated back-and-forth motions
and dynamical heterogeneities on the length scale of the next-neighbor
distance.Comment: 12 pages, 13 figure
A rare localization in right-sided endocarditis diagnosed by echocardiography: A case report
BACKGROUND: Right-sided endocarditis occurs predominantly in intravenous drug users, patients with pacemakers or central venous lines and with congenital heart diseases. The vast majority of cases involve the tricuspid valve. CASE PRESENTATION: A case of a 31-year-old woman with intravenous drug abuse who had a right-sided vegetation attached to the muscular bundle of the right ventricle is presented. Transthoracic echocardiography revealed a vegetation in the right ventricular outflow tract. Transesophageal echocardiography clearly showed that the 1.8 cm vegetation was not adherent to the pulmonary valve but attached to a muscular bundle. CONCLUSIONS: Our case points to an unusual location of right-sided endocarditis in intravenous drug users. It confirms that TTE remains an easy and highly sensitive first-line examination for the diagnosis of right-sided endocarditis
The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection
Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Î2A, Î2B, Î2A/Î2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Î2A and Î2A/Î2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Î2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Î2A and Î2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Î2A virus infection. Infection with Î2A and Î2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Î2A/Î2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al
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