Sila-Riechstoffe und Riechstoffisostere. - XII : Geruchsvergleiche homologer Organoelementverbindungen der vierten Hauptgruppe (C, Si, Ge, Sn)

Homologous compounds of the linalool type R(CH3)2El-OH (with R = C6H5CH2 and C6H5CH2CH2) as well as their derivatives R(CH3)2El-OCH3 and [R(CH3)2El]2O show, in dependence of El = C, Si, Ge and Sn partly similar, but sometimes very different characteristics of odor. Unexpected are high qualities of fragrance with El = Ge, whereas derivatives with El = Sn remain scentless, obviously owing to polymerization. Noteworthy are the strong differences of odor in the system C6H5CH2El(CH3)3 from C via Si and Ge up to Sn, standing fully contrary to the postulation of Amoore whereupon smell qualities are only controlled by size and shape of molecules. C6H5CH2Sn(CH3)2OH (A1Sn) crystallizes as poly-µ-hydroxo-benzyldimethyltin with an one dimensional SnOSnO chain (SnO 2.17(9) and 2.29(9) A°) in the monoclinic space group C2 (a = 12.696(4), b = 4.181(2), c = 10.626(3) A° and ß = 106.8(3)°)

Sila-Riechstoffe und Riechstoffisostere. - XII : Geruchsvergleiche homologer Organoelementverbindungen der vierten Hauptgruppe (C, Si, Ge, Sn)

Homologous compounds of the linalool type R(CH3)2El-OH (with R = C6H5CH2 and C6H5CH2CH2) as well as their derivatives R(CH3)2El-OCH3 and [R(CH3)2El]2O show, in dependence of El = C, Si, Ge and Sn partly similar, but sometimes very different characteristics of odor. Unexpected are high qualities of fragrance with El = Ge, whereas derivatives with El = Sn remain scentless, obviously owing to polymerization. Noteworthy are the strong differences of odor in the system C6H5CH2El(CH3)3 from C via Si and Ge up to Sn, standing fully contrary to the postulation of Amoore whereupon smell qualities are only controlled by size and shape of molecules. C6H5CH2Sn(CH3)2OH (A1Sn) crystallizes as poly-µ-hydroxo-benzyldimethyltin with an one dimensional SnOSnO chain (SnO 2.17(9) and 2.29(9) A°) in the monoclinic space group C2 (a = 12.696(4), b = 4.181(2), c = 10.626(3) A° and ß = 106.8(3)°)

Apertureless scanning near-field optical microscopy of sparsely labeled tobacco mosaic viruses and the intermediate filament desmin

Harder A, Dieding M, Walhorn V, et al. Apertureless scanning near-field optical microscopy of sparsely labeled tobacco mosaic viruses and the intermediate filament desmin. Beilstein Journal of Nanotechnology. 2013;4:510-516.Both fluorescence imaging and atomic force microscopy (AFM) are highly versatile and extensively used in applications ranging from nanotechnology to life sciences. In fluorescence microscopy luminescent dyes serve as position markers. Moreover, they can be used as active reporters of their local vicinity. The dipolar coupling of the tip with the incident light and the fluorophore give rise to a local field and fluorescence enhancement. AFM topographic imaging allows for resolutions down to the atomic scale. It can be operated in vacuum, under ambient conditions and in liquids. This makes it ideal for the investigation of a wide range of different samples. Furthermore an illuminated AFM cantilever tip apex exposes strongly confined non-propagating electromagnetic fields that can serve as a coupling agent for single dye molecules. Thus, combining both techniques by means of apertureless scanning near-field optical microscopy (aSNOM) enables concurrent high resolution topography and fluorescence imaging. Commonly, among the various (apertureless) SNOM approaches metallic or metallized probes are used. Here, we report on our custom-built aSNOM setup, which uses commercially available monolithic silicon AFM cantilevers. The field enhancement confined to the tip apex facilitates an optical resolution down to 20 nm. Furthermore, the use of standard mass-produced AFM cantilevers spares elaborate probe production or modification processes. We investigated tobacco mosaic viruses and the intermediate filament protein desmin. Both are mixed complexes of building blocks, which are fluorescently labeled to a low degree. The simultaneous recording of topography and fluorescence data allows for the exact localization of distinct building blocks within the superordinate structures

Analysis of Cd44-Containing Lipid Rafts: Recruitment of Annexin II and Stabilization by the Actin Cytoskeleton

CD44, the major cell surface receptor for hyaluronic acid (HA), was shown to localize to detergent-resistant cholesterol-rich microdomains, called lipid rafts, in fibroblasts and blood cells. Here, we have investigated the molecular environment of CD44 within the plane of the basolateral membrane of polarized mammary epithelial cells. We show that CD44 partitions into lipid rafts that contain annexin II at their cytoplasmic face. Both CD44 and annexin II were released from these lipid rafts by sequestration of plasma membrane cholesterol. Partition of annexin II and CD44 to the same type of lipid rafts was demonstrated by cross-linking experiments in living cells. First, when CD44 was clustered at the cell surface by anti-CD44 antibodies, annexin II was recruited into the cytoplasmic leaflet of CD44 clusters. Second, the formation of intracellular, submembranous annexin II–p11 aggregates caused by expression of a trans-dominant mutant of annexin II resulted in coclustering of CD44. Moreover, a frequent redirection of actin bundles to these clusters was observed. These basolateral CD44/annexin II–lipid raft complexes were stabilized by addition of GTPγS or phalloidin in a semipermeabilized and cholesterol-depleted cell system. The low lateral mobility of CD44 in the plasma membrane, as assessed with fluorescent recovery after photobleaching (FRAP), was dependent on the presence of plasma membrane cholesterol and an intact actin cytoskeleton. Disruption of the actin cytoskeleton dramatically increased the fraction of CD44 which could be recovered from the light detergent-insoluble membrane fraction. Taken together, our data indicate that in mammary epithelial cells the vast majority of CD44 interacts with annexin II in lipid rafts in a cholesterol-dependent manner. These CD44-containing lipid microdomains interact with the underlying actin cytoskeleton

A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer

Background: Pancreatic cancer is the fourth most common cause of cancer related death in Western countries. Advantages in surgical techniques, radiation and chemotherapy had almost no impact on the long term survival of affected patients. Therefore, the need for better treatment strategies is urgent. HER2, a receptor tyrosine kinase of the EGFR family, involved in signal transduction pathways leading to cell growth and differentiation is overexpressed in a number of cancers, including breast and pancreatic cancer. While in breast cancer HER2 has already been successfully used as a treatment target, there are only limited data evaluating the effects of inhibiting HER2 tyrosine kinases in patients with pancreatic cancer. Methods: Here we report the design of a prospective, non-randomized multi-centered Phase II clinical study evaluating the effects of the Fluoropyrimidine-carbamate Capecitabine (Xeloda (R)) and the monoclonal anti-HER2 antibody Trastuzumab (Herceptin (R)) in patients with non-resectable, HER2 overexpressing pancreatic cancer. Patients eligible for the study will receive Trastuzumab infusions on day 1, 8 and 15 concomitant to the oral intake of Capecitabine from day 1 to day 14 of each three week cylce. Cycles will be repeated until tumor progression. A total of 37 patients will be enrolled with an interim analysis after 23 patients. Discussion: Primary end point of the study is to determine the progression free survival after 12 weeks of bimodal treatment with the chemotherapeutic agent Capecitabine and the anti-HER2 antibody Trastuzumab. Secondary end points include patient's survival, toxicity analysis, quality of life, the correlation of HER2 overexpression and clinical response to Trastuzumab treatment and, finally, the correlation of CA19-9 plasma levels and progression free intervals

A next-generation in-situ nanoprobe beamline for the Advanced Photon Source

The Advanced Photon Source is currently developing a suite of new hard x-ray beamlines, aimed primarily at the study of materials and devices under real conditions. One of the flagship beamlines of the APS Upgrade is the In-Situ Nanoprobe beamline (ISN beamline), which will provide in-situ and operando characterization of advanced energy materials and devices under change of temperature and gases, under applied fields, in 3D. The ISN beamline is designed to deliver spatially coherent x-rays with photon energies between 4 keV and 30 keV to the ISN instrument. As an x-ray source, a revolver-type undulator with two interchangeable magnetic structures, optimized to provide high brilliance throughout the range of photon energies of 4 keV – 30 keV, will be used. The ISN instrument will provide a smallest hard x-ray spot of 20 nm using diffractive optics, with sensitivity to sub-10 nm sample structures using coherent diffraction. Using nanofocusing mirrors in Kirkpatrick-Baez geometry, the ISN will also provide a focus of 50 nm with a flux of 8·1011 Photons/s at a photon energy of 10 keV, several orders of magnitude larger than what is currently available. This will allow imaging of trace amounts of most elements in the periodic table, with a sensitivity to well below 100 atoms for most metals in thin samples. It will also enable nanospectroscopic studies of the chemical state of most materials relevant to energy science. The ISN beamline will be primarily used to study inorganic and organic photovoltaic systems, advanced batteries and fuel cells, nanoelectronics devices, and materials and systems diesigned to reduce the environmental impact of combustion.United States. Dept. of Energy (SunShot Initiative Contract DE-EE0005314)United States. Dept. of Energy (SunShot Initiative Contract DE-EE0005329)United States. Dept. of Energy (SunShot Initiative Contract DE-EE0005948

MetNH3: Metrology for Ammonia in Ambient Air

Measuring ammonia in ambient air is a sensitive and priority issue due to its harmful effects on human health and ecosystems. Ammonia is increasingly being globally acknowledged as a key precursor to atmospheric particulate matter. The European Directive 2001/81/EC on “National Emission Ceilings for Certain Atmospheric Pollutants (NEC)” regulates ammonia emissions in the member states. However, due to the chemical characteristics of ambient ammonia traceable on-line measurements still have significant challenges in analytical technology, uncertainty, quality assurance and quality control (QC/QA). Currently the UK National Ammonia Monitoring Network uses an accredited off-line low temporal resolution and on-line denuder–IC methods at the UK Supersites. There is a need for traceable ammonia measurements which will be vitally important for identifying changes in environment policies, climate and agricultural practice. This in turn should lead to improvements emission inventory uncertainties and for providing independent verification of atmospheric model predictions. MetNH3 (EMRP Joint Research Project) has worked with SMEs in testing improved reference gas mixtures by static and dynamic gravimetric generation methods, develop and refine existing laser based optical spectrometric standards and establishing the transfer from high-accuracy standards to field applicable methods. The first results from the metrological characterisation of a commercially available cavity ring-down spectrometer (CRDS) are presented and the results from a new design “Controlled Atmosphere Test Facility (CATFAC)”, which is currently characterising the performance of diffusive samplers. The range and characteristics of instruments are discussed. The plans for a major ammonia field intercomparison in 2016 will be outlined