NVP‐BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family

Erythropoietin‐producing hepatocellular (EPH) receptors are transmembrane receptor tyrosine kinases. Their extracellular domains bind specifically to ephrin A/B ligands, and this binding modulates intracellular kinase activity. EPHs are key players in bidirectional intercellular signaling, controlling cell morphology, adhesion, and migration. They are increasingly recognized as cancer drug targets. We analyzed the binding of NVP‐BHG712 (NVP) to EPHA2 and EPHB4. Unexpectedly, all tested commercially available NVP samples turned out to be a regioisomer (NVPiso) of the inhibitor, initially described in a Novartis patent application. They only differ by the localization of a single methyl group on either one of two adjacent nitrogen atoms. The two compounds of identical mass revealed different binding modes. Furthermore, both in vitro and in vivo experiments showed that the isomers differ in their kinase affinity and selectivity.     

Performance tradeoffs in structured peer to peer streaming

We consider the following basic question: a source node wishes to stream an ordered sequence of packets to a collection of receivers, which are in K$K$ clusters. A node may send a packet to another node in its own cluster in one time step and to a node in a different cluster in _Tc$T_c$ time steps (_Tc>1)$(T_c>1)$. Each cluster has two special nodes. We assume that the source and the special nodes in each cluster have a higher capacity and thus can send multiple packets at each step, while all other nodes can both send and receive a packet at each step. We construct two (intra-cluster) data communication schemes, one based on multi-trees (using a collection of d$d$-ary interior-disjoint trees) and the other based on hypercubes. The multi-tree scheme sustains streaming within a cluster with O(dlogN)$O(dlogN)$ maximum playback delay and O(dlogN)$O(dlogN)$ size buffers, while communicating with O(d)$O\left(d\right)$ neighbors, where N$N$ is the maximum size of any cluster. We also show that this protocol is optimal when d=2$d=2$ or 3. The hypercube scheme sustains streaming within a cluster, with O(log²(N))$O\left({log}^2\left(N\right)\right)$ maximum playback delay and O(1)$O\left(1\right)$ size buffers, while communicating with O(log(N))$O(log\left(N\right))$ neighbors, for arbitrary N$N$. In addition, we extend our multi-tree scheme to work when receivers depart and arrive over time. We also evaluate our dynamic schemes using simulations.     

The equivalence of two classical list scheduling algorithms for dependent typed tasks with release dates,due dates and precedence delays

We consider a finite set of unit time execution tasks with release dates, due dates and precedence delays. The machines are partitioned into k classes. Each task requires one machine from a fixed class to be executed. The problem is the existence of a feasible schedule. This general problem is known to be \(\mathcal {NP}\)-complete; many studies were devoted to the determination of polynomial time algorithms for some special subcases, most of them based on a particular list schedule. The Garey–Johnson and Leung–Palem–Pnueli algorithms (respectively GJ and LPP in short) are both improving the due dates to build a priority list. They are modifying them using necessary conditions until a fixed point is reached. The present paper shows that these two algorithms are different implementations of the same generic one. The main consequence is that all the results valid for GJ algorithm are also for LPP and vice versa.     

A comprehensive study of the use of advertisements as incentives in P2P streaming systems

P2P streaming systems, such as PPLive and PPStream, have become popular services with the widespread deployment of broadband networks. However, P2P streaming systems still face free-riding problems, similar to those that have been observed in P2P file sharing systems. Thus, one important problem in providing streaming services is that of providing appropriate incentives for peers to contribute their upload capacity. To this end, we propose the use of advertisements as an incentive for peers to contribute upload capacity. In the proposed framework, peers enjoy the same quality of streamed media, with the difference in quality of service being achieved through different amounts of advertisements viewed, based on the resource contributions to the system. Moreover, since calculating peers’ contributions accurately is important to successfully deploying such systems, we design a token-based framework to address this problem. An extensive simulation-based study is performed to evaluate the proposed approach. The results demonstrate that our approach provides appropriate incentives for peers to contribute their resources. Furthermore, we explore several characteristics of the token-based mechanism which can provide system developers with insight into efficient development of such systems.     

Liquid distribution and liquid hold-up in modern high capacity packings

In order to model and optimise industrial gas/liquid contactors such as those used for distillation or for post-combustion capture of CO₂, liquid hold-up and liquid distribution have been measured for two modern high capacity packings, a structured packing and a random packing. A gamma-ray tomographic system has been used to obtain liquid flow maps over a cross section of a 400 mm internal diameter column from which liquid hold-up values can be deduced. It is observed that the liquid flow is homogeneously distributed for both packings, the structured packing giving better results. Correlations are proposed to estimate the liquid hold-up, the effect of the liquid flowrate and the liquid viscosity being taken into account. A non-negligible static liquid hold-up is considered for the structured packing, which can be explained by the texture on the packing walls. As long as there is a little effect of the counter current gas, then below the loading point, results can be extrapolated to larger columns.     

德国科学家利用硅材料研制发光器件

硅是最重要的微电子材料,它具有很好的电子特性和易加工特性.但硅的光学特性远不如其电子特性,因此在制造发光二极管和半导体激光器件时,通常采用较昂贵的砷化镓或磷化铟材料,而不是廉价的硅.最近,德国科学家在研制硅发光器件方面取得了新进展,有望利用廉价硅材料生产发光二极管和半导体激光器件.     

光子技术实现了光纤与硅片的集成

由半导体开发商Luxtera公司（位于美国加利福尼亚州卡尔斯巴德）推出的CMOS光子技术可提供10Gb／s的光调制速率,从而能够将高速光纤接口与采用工业标准CMOS制造工艺所生产的硅器件集成在一起。通过减少昂贵Ⅲ-Ⅴ半导体的用量,该技术可为计算机和通信设备OEM制造商提供光纤通信的性能优势,并使成本和设备复杂性显著下降。     

燃料电池2005年年会探讨业界的最新发展

2005年6月7日至8日在美国明尼苏选州明尼阿波利斯Hyatt Regency Minneapolis举行的燃料电池2005年年会（Fuel Cell 2005）对于那些有兴趣学习和应用燃料电池技术的人们来说是第二次年会。此次为期两天的会议为OEM制造商、设计师、工程师和集成商提供了一个研讨燃料电池、元件、材料以及系统集成方面最新性能的互动式论坛。     

Structure-Based Understanding of ABCA3 Variants

ABCA3 is a crucial protein of pulmonary surfactant biosynthesis, associated with recessive pulmonary disorders such as neonatal respiratory distress and interstitial lung disease. Mutations are mostly private, and accurate interpretation of variants is mandatory for genetic counseling and patient care. We used 3D structure information to complete the set of available bioinformatics tools dedicated to medical decision. Using the experimental structure of human ABCA4, we modeled at atomic resolution the human ABCA3 3D structure including transmembrane domains (TMDs), nucleotide-binding domains (NBDs), and regulatory domains (RDs) in an ATP-bound conformation. We focused and mapped known pathogenic missense variants on this model. We pinpointed amino-acids within the NBDs, the RDs and within the interfaces between the NBDs and TMDs intracellular helices (IHs), which are predicted to play key roles in the structure and/or the function of the ABCA3 transporter. This theoretical study also highlighted the possible impact of ABCA3 variants in the cytosolic part of the protein, such as the well-known p.Glu292Val and p.Arg288Lys variants.     

硅光子技术的新突破

东京理工大学和富士通微电子已经联合开发出用于新一代非易失性铁电随机存储器（Ferroelectric Random Access Memory,FeRAM）的材料和工艺技术。这种改进的铋、铁、氧元素的合成材料（BiFeO3或BFO）能使FeRAM设备的数据存储容量提高到现在容量的五倍。