Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed

An exact sequence for contact- and symplectic homology

A symplectic manifold $W$ with contact type boundary $M = \partial W$ induces a linearization of the contact homology of $M$ with corresponding linearized contact homology $HC(M)$. We establish a Gysin-type exact sequence in which the symplectic homology $SH(W)$ of $W$ maps to $HC(M)$, which in turn maps to $HC(M)$, by a map of degree -2, which then maps to $SH(W)$. Furthermore, we give a description of the degree -2 map in terms of rational holomorphic curves with constrained asymptotic markers, in the symplectization of $M$.Comment: Final version. Changes for v2: Proof of main theorem supplemented with detailed discussion of continuation maps. Description of degree -2 map rewritten with emphasis on asymptotic markers. Sec. 5.2 rewritten with emphasis on 0-dim. moduli spaces. Transversality discussion reorganized for clarity (now Remark 9). Various other minor modification

The Minimal Length of a Lagrangian Cobordism between Legendrians

To investigate the rigidity and flexibility of Lagrangian cobordisms between Legendrian submanifolds, we investigate the minimal length of such a cobordism, which is a $1$-dimensional measurement of the non-cylindrical portion of the cobordism. Our primary tool is a set of real-valued capacities for a Legendrian submanifold, which are derived from a filtered version of Legendrian Contact Homology. Relationships between capacities of Legendrians at the ends of a Lagrangian cobordism yield lower bounds on the length of the cobordism. We apply the capacities to Lagrangian cobordisms realizing vertical dilations (which may be arbitrarily short) and contractions (whose lengths are bounded below). We also study the interaction between length and the linking of multiple cobordisms as well as the lengths of cobordisms derived from non-trivial loops of Legendrian isotopies.Comment: 33 pages, 9 figures. v2: Minor corrections in response to referee comments. More general statement in Proposition 3.3 and some reorganization at the end of Section

Weak and strong fillability of higher dimensional contact manifolds

For contact manifolds in dimension three, the notions of weak and strong symplectic fillability and tightness are all known to be inequivalent. We extend these facts to higher dimensions: in particular, we define a natural generalization of weak fillings and prove that it is indeed weaker (at least in dimension five),while also being obstructed by all known manifestations of "overtwistedness". We also find the first examples of contact manifolds in all dimensions that are not symplectically fillable but also cannot be called overtwisted in any reasonable sense. These depend on a higher-dimensional analogue of Giroux torsion, which we define via the existence in all dimensions of exact symplectic manifolds with disconnected contact boundary.Comment: 68 pages, 5 figures. v2: Some attributions clarified, and other minor edits. v3: exposition improved using referee's comments. Published by Invent. Mat

Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 nuclear bodies

Background: Active pre-mRNA splicing occurs co-transcriptionally, and takes place throughout the nucleoplasm of eukaryotic cells. Splicing decisions are controlled by networks of nuclear RNA-binding proteins and their target sequences, sometimes in response to signalling pathways. Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA) family of RNA-binding proteins, which regulate splicing in response to signalling cascades. Nuclear Sam68 protein is concentrated within subnuclear organelles called SLM/Sam68 Nuclear Bodies (SNBs), which also contain some other splicing regulators, signalling components and nucleic acids. Results: We used proteomics to search for the major interacting protein partners of nuclear Sam68. In addition to Sam68 itself and known Sam68-associated proteins (heterogeneous nuclear ribonucleoproteins hnRNP A1, A2/B1 and G), we identified hnRNP L as a novel Sam68-interacting protein partner. hnRNP L protein was predominantly present within small nuclear protein complexes approximating to the expected size of monomers and dimers, and was quantitatively associated with nucleic acids. hnRNP L spatially co-localised with Sam68 as a novel component of SNBs and was also observed within the general nucleoplasm. Localisation within SNBs was highly specific to hnRNP L and was not shared by the closely-related hnRNP LL protein, nor any of the other Sam68-interacting proteins we identified by proteomics. The interaction between Sam68 and hnRNP L proteins was observed in a cell line which exhibits low frequency of SNBs suggesting that this association also takes place outside SNBs. Although ectopic expression of hnRNP L and Sam68 proteins independently affected splicing of CD44 variable exon v5 and TJP1 exon 20 minigenes, these proteins did not, however, co-operate with each other in splicing regulation of these target exons. Conclusion: Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs

Parameterized Algorithms for Graph Partitioning Problems

We study a broad class of graph partitioning problems, where each problem is specified by a graph $G=(V,E)$, and parameters $k$ and $p$. We seek a subset $U\subseteq V$ of size $k$, such that $\alpha_1m_1 + \alpha_2m_2$ is at most (or at least) $p$, where $\alpha_1,\alpha_2\in\mathbb{R}$ are constants defining the problem, and $m_1, m_2$ are the cardinalities of the edge sets having both endpoints, and exactly one endpoint, in $U$, respectively. This class of fixed cardinality graph partitioning problems (FGPP) encompasses Max $(k,n-k)$-Cut, Min $k$-Vertex Cover, $k$-Densest Subgraph, and $k$-Sparsest Subgraph. Our main result is an $O^*(4^{k+o(k)}\Delta^k)$ algorithm for any problem in this class, where $\Delta \geq 1$ is the maximum degree in the input graph. This resolves an open question posed by Bonnet et al. [IPEC 2013]. We obtain faster algorithms for certain subclasses of FGPPs, parameterized by $p$, or by $(k+p)$. In particular, we give an $O^*(4^{p+o(p)})$ time algorithm for Max $(k,n-k)$-Cut, thus improving significantly the best known $O^*(p^p)$ time algorithm

The introduction of Corded Ware Culture at a local level: an exploratory study of cultural change during the Late Neolithic of the Dutch West Coast through ceramic technology

The introduction of the Corded Ware Culture (3000–2500 BCE) is considered a formative event in Europe's past. Ancient DNA analyses demonstrate that migrations played a crucial role in this event. However, these analyses approach the issue at a supra-regional scale, leaving questions about the regional and local impact of this event unresolved. This study pilots an approach to ceramics that brings this small-scale impact into focus by using the transmission of ceramic technology as a proxy for social change. It draws on ethno-archaeological studies of the effects of social changes on the transmission of ceramic production techniques to hypothesise the impact of three idealised scenarios that archaeologists have proposed for the introduction of Corded Ware Culture: migration, diffusion, and network interactions. Subsequently, it verifies these hypotheses by integrating geochemical (WDXRF), mineralogical (petrography), and macromorphological analysis of ceramics with network analysis. This method is applied to 30 Late Neolithic ceramic vessels from three sites in the western coastal area of the Netherlands (Hazerswoude-Rijndijk N11, Zandwerven, and Voorschoten-De Donk). This study concludes that the introduction of Corded Ware material culture is a process that varies from site to site in the western coastal area of the Netherlands. Moreover, the introduction of the Corded Ware Culture is characterised by continuity in technological traditions throughout the study area, indicating a degree of social continuity despite typological changes in ceramics

Maser Oscillation in a Whispering-Gallery-Mode Microwave Resonator

We report the first observation of above-threshold maser oscillation in a whispering-gallery(WG)-mode resonator, whose quasi-transverse-magnetic, 17th azimuthal-order WG mode, at a frequency of approx. 12.038 GHz, with a loaded Q of several hundred million, is supported on a cylinder of mono-crystalline sapphire. An electron spin resonance (ESR) associated with Fe3+ ions, that are substitutively included within the sapphire at a concentration of a few parts per billion, coincides in frequency with that of the (considerably narrower) WG mode. By applying a c.w. `pump' to the resonator at a frequency of approx. 31.34 GHz, with no applied d.c. magnetic field, the WG (`signal') mode is energized through a three-level maser scheme. Preliminary measurements demonstrate a frequency stability (Allan deviation) of a few times 1e-14 for sampling intervals up to 100 s.Comment: REVTeX v.4, 3 pages, with a separate .bbl file and 3 .eps figure

Blood histamine levels (BHL) in infants and children with respiratory and non-respiratory diseases.

BACKGROUND: Blood histamine levels are decreased after severe allergic reactions and in various chronic diseases. AIMS: To study blood histamine levels in infants and children with acute infectious and non-infectious, non-allergic, disease. METHODS: Blood histamine levels were investigated by a fluorometric method in infants and children admitted to hospital with bronchiolitis, non-wheezing bronchitis, acute infections of the urinary tract, skin and ear-nose-throat, gastroenteritis, or hyperthermia of unknown aetiology. Results of blood histamine levels and white blood cell counts were compared with those obtained for children recovering from benign non-infectious, non-allergic illnesses. RESULTS: As compared with control children, white blood cell numbers were significantly increased in children with acute infections of the urinary tract, skin and ear-nose-throat, and were significantly decreased in children with gastroenteritis. Blood histamine levels were significantly lower in children with gastroenteritis and hyperthermia than in children with other diseases and control children. It was not possible to correlate blood histamine levels and the number of blood basophils. CONCLUSIONS: BHL are significantly decreased in infants and children with acute gastroenteritis and hyperthermia of unknown aetiology. The mechanisms responsible for the decrease in blood histamine levels in children with gastroenteritis and hyperthermia are discussed