A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

Efficiency improvements in US office equipment: Expected policy impacts and uncertainties

We create a business as usual scenario for office equipment electricity use from industry forecasts of equipment sales, surveys of equipment densities by building type, measured data on wattage and usage by equipment type and projected lifetimes for equipment. We then calculate electricity used by building type and equipment type for Energy Star and advanced scenarios and explore the sensitivity of these results to variations in key input parameters. According to our analysis, the Energy Star programme will save the US almost US$1 billion annually starting in the year 2000, with minimal expenditure of public funds.     

IV-Controlling in einem Systemhaus

This paper analyses the characteristics of software houses as service providers. The tasks of internal IT-services are determined from these characteristics and a reporting system for the IT-controlling is outlined. The concept results from the analysis of one of the 25 largest German software houses. The paper concludes with a case study of the fiscal year 2000 IT-controlling report of the above-mentioned firm.     

低成本手机市场将取得爆炸式增长

目前,低成本手机数量不断增多,市场份额越来越大,比高端手机更受欢迎。研究表明,未来三年,低成本手机市场还将持续增长,这将是无线产业最主要的发展趋势之一,已经并将继续为无线手机制造商、服务供应商及芯片设计商带来金融、市场、战略和技术领域的重大变革与挑战。     

On-line H NMR spectroscopic investigation of hydrogen bonding in supercritical and near critical CO2–methanol up to 35 MPa and 403 K

On-line NMR spectroscopy can beneficially be applied to studies of supercritical and near-critical fluids as an alternative to optical spectroscopy. Up to now high pressure NMR experiments are predominantly accomplished using custom made NMR batch reactors. The authors present a novel high pressure cell with displacement plunger for on-line NMR experiments on compressible fluids which can be used in conjunction with commercially available SCF NMR flow probes. The on-line technique offers advantages compared to stopped flow techniques such as enhanced control of mixture composition and reaction parameters as well as the facility of engagement into the reaction. The new apparatus is used for NMR studies on hydrogen bonding of methanol in near critical and supercritical carbon dioxide up to 403 K and 35 MPa for which data on the chemical shift of the hydroxyl group and methyl group are reported and interpreted.     

In Google We Trust: Users' Decisions on Rank, Position, and Relevance

An eye tracking experiment revealed that college student users have substantial trust in Google's ability to rank results by their true relevance to the query. When the participants selected a link to follow from Google's result pages, their decisions were strongly biased towards links higher in position even if the abstracts themselves were less relevant. While the participants reacted to artificially reduced retrieval quality by greater scrutiny, they failed to achieve the same success rate. This demonstrated trust in Google has implications for the search engine's tremendous potential influence on culture, society, and user traffic on the Web.     

“No-background” maximum likelihood analysis in HBT interferometry

We present a new “no-background” procedure, based on the maximum likelihood method, for fitting the space-time size parameters of the particle production region in ultra-relativistic heavy ion collisions. This procedure uses an approximation to avoid the necessity of constructing a mixed-event background before fitting the data.