Elastic properties of the Non-Fermi liquid metal CeRu4Sb12Ce Ru_4 Sb_{12} and the Dense Kondo semiconductor CeOs4Sb12Ce Os_4 Sb_{12}

We have investigated the elastic properties of the Ce-based filled skutterudite antimonides CeRu$_{4}$Sb$_{12}$ and CeOs$_{4}$Sb$_{12}$ by means of ultrasonic measurements. CeRu$_{4}$Sb$_{12}$ shows a slight increase around 130 K in the temperature dependence of the elastic constants $C$$_{11}$, ($C$$_{11}$-$C$$_{12}$)/2 and $C$$_{44}$. No apparent softening toward low temperature due to a quadrupolar response of the 4$f$-electronic ground state of the Ce ion was observed at low temperatures. In contrast CeOs$_{4}$Sb$_{12}$ shows a pronounced elastic softening toward low temperature in the longitudinal $C$$_{11}$ as a function of temperature ($T$) below about 15 K, while a slight elastic softening was observed in the transverse $C$$_{44}$ below about 1.5 K. Furthermore, CeOs$_{4}$Sb$_{12}$ shows a steep decrease around a phase transition temperature of 0.9 K in both $C$$_{11}$ and$C$$_{44}$. The elastic softening observed in $C$$_{11}$ below about 15 K cannot be explained reasonably only by the crystalline electric field effect. It is most likely to be responsible for the coupling between the elastic strain and the quasiparticle band with a small energy gap in the vicinity of Fermi level. The elastic properties and the 4$f$ ground state of Ce ions in CeRu$_{4}$Sb$_{12}$ and CeOs$_{4}$Sb$_{12}$ are discussed from the viewpoint of the crystalline electric field effect and the band structure in the vicinity of Fermi level.Comment: 9 pages, 11 figures, regular pape

DOC2B: A Novel Syntaxin-4 Binding Protein Mediating Insulin-Regulated GLUT4 Vesicle Fusion in Adipocytes

OBJECTIVE— Insulin stimulates glucose uptake in skeletal muscle and adipose tissues primarily by stimulating the translocation of vesicles containing a facilitative glucose transporter, GLUT4, from intracellular compartments to the plasma membrane. The formation of stable soluble N-ethyl-maleimide–sensitive fusion protein [NSF] attachment protein receptor (SNARE) complexes between vesicle-associated membrane protein-2 (VAMP-2) and syntaxin-4 initiates GLUT4 vesicle docking and fusion processes. Additional factors such as munc18c and tomosyn were reported to be negative regulators of the SNARE complex assembly involved in GLUT4 vesicle fusion. However, despite numerous investigations, the positive regulators have not been adequately clarified

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

Reconfigurable SDM switching using novel silicon photonic integrated circuit

Space division multiplexing using multicore fibers is becoming a more and more promising technology. In space-division multiplexing fiber network, the reconfigurable switch is one of the most critical components in network nodes. In this paper we for the first time demonstrate reconfigurable space-division multiplexing switching using silicon photonic integrated circuit, which is fabricated on a novel silicon-on-insulator platform with buried Al mirror. The silicon photonic integrated circuit is composed of a 7 × 7 switch and low loss grating coupler array based multicore fiber couplers. Thanks to the Al mirror, grating couplers with ultra-low coupling loss with optical multicore fibers is achieved. The lowest total insertion loss of the silicon integrated circuit is as low as 4.5 dB, with low crosstalk lower than −30 dB. Excellent performances in terms of low insertion loss and low crosstalk are obtained for the whole C-band. 1 Tb/s/core transmission over a 2-km 7-core fiber and space-division multiplexing switching is demonstrated successfully. Bit error rate performance below 10−9 is obtained for all spatial channels with low power penalty. The proposed design can be easily upgraded to reconfigurable optical add/drop multiplexer capable of switching several multicore fibers

Extended lymph node dissection for gastric cancer from a European perspective

Surgical oncolog

Evaluation of Two Models for Human Topoisomerase I Interaction with dsDNA and Camptothecin Derivatives

Human topoisomerase I (Top1) relaxes supercoiled DNA during cell division. Camptothecin stabilizes Top1/dsDNA covalent complexes which ultimately results in cell death, and this makes Top1 an anti-cancer target. There are two current models for how camptothecin and derivatives bind to Top1/dsDNA covalent complexes (Staker, et al., 2002, Proc Natl Acad Sci USA 99: 15387–15392; and Laco, et al., 2004, Bioorg Med Chem 12: 5225–5235). The interaction energies between bound camptothecin, and derivatives, and Top1/dsDNA in the two models were calculated. The published structure-activity-relationships for camptothecin and derivatives correlated with the interaction energies for camptothecin and derivatives in the Laco et al. model, however, this was not the case for several camptothecin derivatives in the Stacker et al. model. By defining the binding orientation of camptothecin and derivatives in the Top1/dsDNA active-site these results allow for the rational design of potentially more efficacious camptothecin derivatives

Identification and Replication of Loci Involved in Camptothecin-Induced Cytotoxicity Using CEPH Pedigrees

To date, the Centre d'Etude Polymorphism Humain (CEPH) cell line model has only been used as a pharmacogenomic tool to evaluate which genes are responsible for the disparity in response to a single drug. The purpose of this study was demonstrate the model's ability to establish a specific pattern of quantitative trait loci (QTL) related to a shared mechanism for multiple structurally related drugs, the camptothecins, which are Topoisomerase 1 inhibitors. A simultaneous screen of six camptothecin analogues for in vitro sensitivity in the CEPH cell lines resulted in cytotoxicity profiles and orders of potency which were in agreement with the literature. For all camptothecins studied, heritability estimates for cytotoxic response averaged 23.1±2.6%. Nonparametric linkage analysis was used to identify a relationship between genetic markers and response to the camptothecins. Ten QTLs on chromosomes 1, 3, 5, 6, 11, 12, 16 and 20 were identified as shared by all six camptothecin analogues. In a separate validation experiment, nine of the ten QTLs were replicated at the significant and suggestive levels using three additional camptothecin analogues. To further refine this list of QTLs, another validation study was undertaken and seven of the nine QTLs were independently replicated for all nine camptothecin analogues. This is the first study using the CEPH cell lines that demonstrates that a specific pattern of QTLs could be established for a class of drugs which share a mechanism of action. Moreover, it is the first study to report replication of linkage results for drug-induced cytotoxicity using this model. The QTLs, which have been identified as shared by all camptothecins and replicated across multiple datasets, are of considerable interest; they harbor genes related to the shared mechanism of action for the camptothecins, which are responsible for variation in response

Cambridge quantum network

AbstractFuture-proofing current fibre networks with quantum key distribution (QKD) is an attractive approach to combat the ever growing breaches of data theft. To succeed, this approach must offer broadband transport of quantum keys, efficient quantum key delivery and seamless user interaction, all within the existing fibre network. However, quantum networks to date either require dark fibres and/or offer bit rates inadequate for serving a large number of users. Here we report a city wide high-speed metropolitan QKD network—the Cambridge quantum network—operating on fibres already populated with high-bandwidth data traffic. We implement a robust key delivery layer to demonstrate essential network operation, as well as enabling encryption of 100 Gigabit per second (Gbps) simultaneous data traffic with rapidly refreshed quantum keys. Network resilience against link disruption is supported by high-QKD link rates and network link redundancy. We reveal that such a metropolitan network can support tens of thousands of users with key rates in excess of 1 kilobit per second (kbps) per user. Our result hence demonstrates a clear path for implementing quantum security in metropolitan fibre networks.</jats:p