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All known methods for solid-phase synthesis of molecular arrays exploit positioning techniques to deposit monomers on a substrate preferably high densely. In this paper, stochastic patterning of molecule spots (250 000 spots monomers/cm 2 ) via random allocation of the microbeads on a microstructured glass is presented. The size and shape of the microbeads and the microcavities are selected in such a way so that only one microbead can fit into the respective microcavity. Each microbead can be loaded with a certain type of molecule e.g. amino acids and is brought in the microcavities stochastically. Applying solvent vapor and heating the substrate, the molecules are released from the microbeads and coupled to the functionalized substrate. To differentiate between the microbeads carrying different molecules, quantum dot labels are preliminary introduced into the microbeads. Fluorescence imaging and subsequent data analysis enable decoding of the molecule deposition patterns. After the coupling step is completed, the microbeads are mechanically removed from the microwells. The composition of the monomer microbeads, their deposition and the conditions of the monomer extraction are studied. The stochastic monomer patterning may be used to design novel molecular arrays.

We show here that the number of single-chain antibody fragments (scFv) presented on filamentous phage particles generated with antibody display phagemids can be increased by more than two orders of magnitude by using a newly developed helper phage (hyperphage). Hyperphage have a wild-type pIII phenotype and are therefore able to infect F + Escherichia coli cells with high efficiency; however, their lack of a functional pIII gene means that the phagemid-encoded pIII–antibody fusion is the sole source of pIII in phage assembly. This results in an considerable increase in the fraction of phage particles carrying an antibody fragment on their surface. Antigen-binding activity was increased about 400-fold by enforced oligovalent antibody display on every phage particle. When used for packaging a universal human scFv library, hyperphage improved the specific enrichment factor obtained when panning on tetanus toxin. After two panning rounds, more than 50% of the phage were found to bind to the antigen, compared to 3% when conventional M13KO7 helper phage was used. Thus, hyperphage is particularly useful in stoichiometric situations, when there is little chance that a single phage will locate the desired antigen.

High-resolution radio measurements of air showers—cascades of secondary particles in the atmosphere initiated by cosmic rays—reveal that cosmic rays with energies of 10 17 –10 17.5 electronvolts have a mixed composition, with light elements (protons and helium nuclei) making up 80 per cent of their mass. Mass composition of cosmic rays Stijn Buitink et al . report on the mass composition of cosmic rays in the energy range 10 17 to 10 17.5 electron volts, derived from LOFAR radio telescope measurements of cosmic ray initiated cascades of secondary particles (air showers) in the atmosphere. They find a mixed composition, containing a light-mass fraction of approximately 80%. Unless the extragalactic cosmic ray component becomes significant below 10 17.5 electron volts, these findings indicate an additional Galactic component dominating in this energy range. Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10 17 –10 18 electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal 1 comes from accelerators capable of producing cosmic rays of these energies 2 . Cosmic rays initiate air showers—cascades of secondary particles in the atmosphere—and their masses can be inferred from measurements of the atmospheric depth of the shower maximum 3 ( X max ; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground 4 . Current measurements 5 have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays 6 , 7 , 8 is a rapidly developing technique 9 for determining X max (refs 10 , 11 ) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front 6 , 12 . Here we report radio measurements of X max with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10 17 –10 17.5 electronvolts. This high resolution in X max enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10 17.5 electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10 17 –10 17.5 electronvolt range.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10 17 –10 18 electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal 1 comes from accelerators capable of producing cosmic rays of these energies 2 . Cosmic rays initiate air showers—cascades of secondary particles in the atmosphere—and their masses can be inferred from measurements of the atmospheric depth of the shower maximum 3 ( X max ; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground 4 . Current measurements 5 have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays 6, 7, 8 is a rapidly developing technique 9 for determining X max (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front 6, 12 . Here we report radio measurements of X max with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10 17 –10 17.5 electronvolts. This high resolution in X max enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10 17.5 electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10 17 –10 17.5 electronvolt range.

Recent studies revealed an immunoregulatory role of natural IgG-anti-F(ab′)2 antibodies in both healthy individuals and patients with certain diseases. The implication of anti-F(ab′)2 antibodies in the pathogenesis of diseases prompted us to study the gene segment structure of their antigen-binding domains and their binding characteristics. cDNA was prepared from the lymphocytes of a patient with a high IgG-anti-F(ab′)2 serum titer. Variable heavy and light gene segments were amplified by PCR and inserted into a phagemid surface expression vector. Single-chain antibodies displayed on the phage surface were screened for binding to F(ab′)2 fragments. The subsequent analysis of 95 single clones demonstrated that they all bound specifically to F(ab′)2. Sequence analyses of 12 clones showed that 11 were identical and 1 contained a silent point mutation in the heavy chain and three amino acid exchanges in the light chain. The heavy chains belonged to the VH3 and the light chains to the Vκ2 gene family. The 11 identical light-chain genes were completely homologous to a germ-line sequence (DPK-15). Binding assays showed that the single-chain antibodies bind to F(ab′)2, but not to Fab, Fc, or intact IgG. This binding pattern was confirmed by surface plasmon resonance studies, which revealed a relatively high affinity (Ka = 2.8 × 107 M-1). The strong binding capacity was further demonstrated by competitive inhibition of the serum anti-IgG antibody's interaction with antigen. The present study defines for the first time to our knowledge the gene segment structure of the antigen-binding domain of two human IgG-anti-F(ab′)2 autoantibody clones and describes the binding kinetics of the purified monomeric fragments.

A generic transformation of XML data into the Resource Description Framework (RDF) and its implementation by XSLT transformations is presented. It was developed by the grid integration project for robotic telescopes of AstroGrid-D to provide network communication through the Remote Telescope Markup Language (RTML) to its RDF based information service. The transformation's generality is explained by this example. It automates the transformation of XML data into RDF and thus solves this problem of semantic computing. Its design also permits the inverse transformation but this is not yet implemented.

The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light. An alternative approach is to study the absorption features imprinted on the gamma-ray spectra of distant extragalactic objects by interactions of those photons with the background light photons. Here we report the discovery of gamma-ray emission from the blazars H 2356 -309 and 1ES 1101 -232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources- in particular from the first stars formed. This result also indicates that intergalactic space is more transparent to gamma-rays than previously thought.

The source of Galactic cosmic rays (with energies up to 1015 eV) remains unclear, although it is widely believed that they originate in the shock waves of expanding supernova remnants. At present the best way to investigate their acceleration and propagation is by observing the gamma-rays produced when cosmic rays interact with interstellar gas. Here we report observations of an extended region of very-high-energy ( 1011 eV) gamma-ray emission correlated spatially with a complex of giant molecular clouds in the central 200 parsecs of the Milky Way. The hardness of the gamma-ray spectrum and the conditions in those molecular clouds indicate that the cosmic rays giving rise to the gamma-rays are likely to be protons and nuclei rather than electrons. The energy associated with the cosmic rays could have come from a single supernova explosion around 104 years ago.[PUBLICATION ABSTRACT]