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The immunomodulatory molecule Salp15 is originally described in Ixodes scapularisand has been shown to inhibit CD4 T cell activation. Many Salp15 homologs have been described from Ixodesspecies, and all were well conserved at C-terminal residues that seem to be essential for the function of the protein. In this study, a gene sequence was amplified from cDNA isolated from engorged female I. ricinusticks, which was predicted to generate a protein of 12.3kDa. The protein displayed distinct amino acid differences from previously described I. ricinusSalp15 homologs, with amino acid identity ranging between 46.6% and 93.9%. It was referred to as I. ricinusSalp15-like protein. The protein showed 48.1% sequence identity to I. scapularisSalp15.

According to the ITRS roadmap, semiconductor industry drives the 193nm lithography to its limits, using techniques like double exposure, double patterning, mask-source optimization and inverse lithography. For photomask metrology this translates to full in-die measurement capability for registration and critical dimension together with challenging specifications for repeatability and accuracy. Especially, overlay becomes more and more critical and must be ensured on every die. For this, Carl Zeiss SMS has developed the next generation photomask registration and overlay metrology tool PROVE® which serves the 32nm node and below and which is already well established in the market. PROVE® features highly stable hardware components for the stage and environmental control. To ensure in-die measurement capability, sophisticated image analysis methods based on 2D correlations have been developed. In this paper we demonstrate the in-die capability of PROVE® and present corresponding measurement results for shortterm and long-term measurements as well as the attainable accuracy for feature sizes down to 85nm using different illumination modes and mask types. Standard measurement methods based on threshold criteria are compared with the new 2D correlation methods to demonstrate the performance gain of the latter. In addition, mask-to-mask overlay results of typical box-in-frame structures down to 200nm feature size are presented. It is shown, that from overlay measurements a reproducibility budget can be derived that takes into account stage, image analysis and global effects like mask loading and environmental control. The parts of the budget are quantified from measurement results to identify critical error contributions and to focus on the corresponding improvement strategies.

The new photomask registration and overlay metrology system PROVETMat Carl Zeiss has been developed and already delivered to customers to meet the increased industry requirements for pattern registration tools in terms of resolution and in-die measurement capability. Main drivers of the tool performance specifications are double exposure and double patterning approaches which will help to extend the 193nm lithography platforms while keeping the semiconductor industry conform to ITRS roadmap requirements. To guarantee the demanding tool performance, PROVETMfeatures highly stable hardware components for the stage and environmental control. Moreover, sophisticated image analysis algorithms as for instance correlation methods have been developed to overcome limitations of standard approaches. In this paper we focus on mask-to-mask overlay metrology as one of the critical components of modern lithography. To achieve the challenging requirements with the PROVETMtool, an overlay reproducibility budget is prepared that takes into account stage, image analysis and global effects like mask loading and environmental control. The corresponding parts of the budget are quantified by means of PROVETMoverlay measurements, performed on typical box-in-frame structures. This allows the identification of critical error contributions and the corresponding improvement strategies. In particular, it will be shown, that the new developed correlation methods of PROVETMwill significantly reduce image analysis and camera noise contributions.

In utero and/or childhood environmental tobacco smoke exposure is well known to adversely affect lung function and to depreciate child's health in many ways. Fewer studies have assessed the long-term effects on COPD development and disease severity in later adulthood. COPD patients were interviewed using a structured questionnaire regarding their personal as well as the smoking habits of their parents. Data were compared with the disease history, e.g. COPD exacerbation rate, and their lung function data. Between 2003 and 2004 COPD patients were recruited a) in a private practice specialized in pulmonary medicine (n = 133) and b) in a hospital (n = 158). 75% of their fathers and only 15.4 of all mothers smoked regularly. COPD patients from smoking mothers had lower FEV1 predicted than those raised in household without maternal smoking exposure: 39.4 ± 9.5% vs. 51.9 ± 6.0% (P = 0.037). Fathers had no effect on FEV1 regardless if they are smokers or non-smokers. Rate of severe exacerbations requiring hospitalization remained unaffected by parental second hand smoke exposure. Maternal smoking negatively affects lung function of their offspring even in late adulthood when they develop COPD. It even aggravates the cumulative effect of active cigarette consumption. Clinical course of the COPD remained unaffected.

A number of Theileria annulatagenes have been cloned, sequenced and expressed, including TaSP, TaD, TaSE and TamtHSP70. Several recent publications document the suitability of the recombinant TaSP protein for use in the diagnosis of tropical theileriosis. To investigate whether TaD, TaSE or TamtHSP70 elicit a humoural immune response in the T. annulata-infected host and to assess the potential of these proteins for development of diagnostics, a total of 156 field sera from Sudan and 49 negative sera from Germany were investigated in ELISA for the presence of specific antibodies against these recombinant proteins in comparison to TaSP. Antibodies against TaD and TaSE were found to be present, whereas no antibody response could be detected against the recombinant TamtHSP70. Highest titres were found to be present against the TaSP protein, with antibody titres against TaD and TaSE being in general somewhat lower. Correlation analysis showed a significant correlation of TaSP and TaSE and of TaSE and TaD antibody titres, however not between TaSP and TaD. In conclusion, the infected bovine host was shown to produce antibodies against three of the four recombinant T. annulataproteins tested, all three having been described or predicted to be parasite membrane proteins. The outstanding performance of the TaSP protein for detection of T. annulatainfection in indirect ELISA was confirmed.

Theileriasp. (China) causes severe limitations on the development of the livestock industry in the north-west of China. An enzyme-linked immunosorbent assay (ELISA) based on merozoite homogenate of the parasite for diagnosis of infection has been established; however, cross-reactivity with other small ruminant-infecting piroplasms could not be excluded. Thus, a prerequisite for epidemiological surveys and diagnosis was the establishment of a recombinant protein-based ELISA. To this end, serum from Theileriasp. (China)-infected sheep was used to screen a Theileria lestoquardiexpression library, resulting in the identification of a specifically reacting clone with a high identity to the heat shock protein 70 (HSP70) of Theileria parvaand Theileria annulataand thus named TlHSP70. An HSP70 homologue was also confirmed to be expressed by Theileriasp. (China) merozoites (TcHSP70). A part of the TlHSP70 protein, found to be conserved in TcHSP70, was recombinantly expressed and used to establish an ELISA. A total of 260 field serum samples tested resulted in a sensitivity and specificity of 94.3 and 89.5%, respectively, in comparison with the merozoite homogenate ELISA. The potentials of the application of the test in epidemiological surveys to map out the prevalence of the disease and for routine diagnostics are described.Theileriasp. (China) causes severe limitations on the development of the livestock industry in the north-west of China. An enzyme-linked immunosorbent assay (ELISA) based on merozoite homogenate of the parasite for diagnosis of infection has been established; however, cross-reactivity with other small ruminant-infecting piroplasms could not be excluded. Thus, a prerequisite for epidemiological surveys and diagnosis was the establishment of a recombinant protein-based ELISA. To this end, serum from Theileriasp. (China)-infected sheep was used to screen a Theileria lestoquardiexpression library, resulting in the identification of a specifically reacting clone with a high identity to the heat shock protein 70 (HSP70) of Theileria parvaand Theileria annulataand thus named TlHSP70. An HSP70 homologue was also confirmed to be expressed by Theileriasp. (China) merozoites (TcHSP70). A part of the TlHSP70 protein, found to be conserved in TcHSP70, was recombinantly expressed and used to establish an ELISA. A total of 260 field serum samples tested resulted in a sensitivity and specificity of 94.3 and 89.5%, respectively, in comparison with the merozoite homogenate ELISA. The potentials of the application of the test in epidemiological surveys to map out the prevalence of the disease and for routine diagnostics are described.

Permanent in vivo verification of IMRT photon beam profiles by a radiation detector with spatial resolution, positioned on the radiation entrance side of the patient, has not been clinically available so far. In this work we present the DAVID system, which is able to perform this quality assurance measurement while the patient is treated. The DAVID system is a flat, multi-wire transmission-type ionization chamber, placed in the accessory holder of the linear accelerator and constructed from translucent materials in order not to interfere with the light field. Each detection wire of the chamber is positioned exactly in the projection line of a MLC leaf pair, and the signal of each wire is proportional to the line integral of the ionization density along this wire. Thereby, each measurement channel essentially presents the line integral of the ionization density over the opening width of the associated leaf pair. The sum of all wire signals is a measure of the dose-area product of the transmitted photon beam and of the total radiant energy administered to the patient. After the dosimetric verification of an IMRT plan, the values measured by the DAVID system are stored as reference values. During daily treatment the signals are re-measured and compared to the reference values. A warning is output if there is a deviation beyond a threshold. The error detection capability is a leaf position error of less than 1 mm for an isocentric 1 cm 1 cm field, and of 1 mm for an isocentric 20 cm 20 cm field.

The authors sought to quantify the influence of the CYP3A and P‐glycoprotein inhibitor ketoconazole on the pharmacokinetics of everolimus in healthy subjects. This was a 2‐period, single‐sequence, crossover study in 12 healthy subjects. In period 1, subjects received the reference treatment of a single 2‐mg dose of everolimus. In period 2, they received the test treatment of ketoconazole 200 mg twice daily for a total of 8 days and a single dose of everolimus coadministered on the fourth day of ketoconazole therapy. The test/reference ratio and 90% confidence interval were derived for everolimus maximum concentration and area under the curve. During ketoconazole coadministration, everolimus maximum concentration increased 3.9‐fold (90% confidence interval, 3.4–4.6) from 15 ± 4 ng/mL to 59 ± 13 ng/mL. Everolimus area under the curve increased 15.0‐fold (90% confidence interval, 13.6–16.6) from 90 ± 23 ng•h/mL to 1324 ± 232 ng•h/mL. Everolimus half‐life was prolonged by 1.9‐fold from 30 ± 4 hours to 56 ± 5 hours. Everolimus did not appear to alter ketoconazole predose concentrations. Given the magnitude of this drug interaction, use of ketoconazole should be avoided if possible in everolimus‐treated patients.

The recombinant surface protein of Theileria annulata (TaSP) was used in the standardization and validation of an enzyme linked immunosorbent assay (ELISA) for the detection of circulating antibodies against tropical theileriosis. ELISA data were expressed as the percentage positivity (PP) of the reactivity of an internal positive control. A total of 50 sera samples from a disease-free area were used for the calculation of the cut-off value which served as a threshold between the positive and the negative sera samples. This was determined as the mean PP plus two standard deviations or the twice the mean PP of the results obtained with these negative samples. The obtained thresholds were 17.8% and 18.3%, respectively. Accordingly, the reactivity of 140 field sera samples collected at random from an area known to be endemic for tropical theileriosis in Sudan was determined as PP values which were then compared to the results obtained using the indirect fluorescence antibody test (IFAT) from the same samples. Both tests showed a high degree of correlation. The TaSP-ELISA had a sensitivity of 99.1% and specificity of 90.47% when taking the IFAT as a reference test. Our test has proved its suitability for the diagnosis of tropical theileriosis and could be used in serological surveys to map out the prevalence of the disease or to monitor vaccination efficiencies in disease-free populations.

ABSTRACTTAN 1057-resistant Staphylococcus aureusand Escherichia colistrains were selected to elucidate the mechanism of resistance and the mode of action of this dipeptide antibiotic. Cell-free translation with isolated ribosomes and S150 fractions from sensitive and resistant S. aureusstrains demonstrated that alterations in the ribosomes contribute to the resistance of the bacteria.

In the present study, we identified a gene from Theileria lestoquardiand from a recently described Theileriaspecies which is highly pathogenic for small ruminants in China. Since the taxonomic position of the latter parasite is still not clear, we refer to it as Theileria(China) species. The gene described here comprises an open reading frame of about 948 bp which prospectively encodes a 35-kDa protein. Its sequence is most closely related to the polymorphic immunodominant membrane protein of T. parva(36% identity). A search for sequence patterns and motifs within the predicted amino acid sequence revealed that this gene possesses three membrane-spanning regions at its C-terminal part, suggesting that it is a membrane protein. Several allelic variants of this gene were found in each parasite species, demonstrating interspecies and intraspecies variation. The predicted amino acid sequence variants display a substantial size and sequence polymorphism in the central part of its presumed extracellular region, while the N-terminal and the transmembrane/intracellular regions are highly conserved.

This paper studies multiproduct inventory models with stochastic demands and a warehousing constraint. Finite horizon as well as stationary and nonstationary discounted-cost infinite-horizon problems are addressed. Existence of optimal feedback policies is established under fairly general assumptions. Furthermore, the structure of the optimal policies is analyzed when the ordering cost is linear and the inventory/backlog cost is convex. The optimal policies generalize the base-stock policies in the single-product case. Finally, in the stationary infinite-horizon case, a myopic policy is proved to be optimal if the product demands are independent and the cost functions are separable.

This paper revisits the classical papers of Iglehart (Ref. 1) and Veinott and Wagner (Ref. 2) devoted to stochastic inventory problems with the criterion of long-run average cost minimization. We indicate some of the assumptions that are used implicitly without verification in their stationary distribution approach to the problems and provide the missing (nontrivial) verification. In addition to completing their analysis, we examine the relationship between the stationary distribution approach and the dynamic programming approach to the average-cost stochastic inventory problems.

Polymeric core-shell systems were produced by a two-stage emulsion polymerization technique under fixed conditions: i) monodisperse seed latex with a sufficiently high particle number; ii) starved monomer-II addition; iii) water-soluble initiator; iv) incompatibility of core and shell polymer. From electron micrographs, it is not possible to determine where the second polymer is located within these two-stage emulsion polymers. The internal structure of the particles can be detected by small-angle x-ray scattering. The results indicate that; i) the emulsion polymerization process takes place in a small surface layer region of the seed particles, and ii) a small interfacial layer exists between the core and shell polymer.

This paper studies stochastic inventory problems with unbounded Markovian demands, ordering costs that are lower semicontinuous, and inventory/backlog (or surplus) costs that are lower semicontinuous with polynomial growth. Finite-horizon problems, stationary and nonstationary discounted-cost infinite-horizon problems, and stationary long-run average-cost problems are addressed. Existence of optimal Markov or feedback policies is established. Furthermore, optimality of (s, S)-type policies is proved when, in addition, the ordering cost consists of fixed and proportional cost components and the surplus cost is convex.

Layers from poly[(1-methylvinyl isocyanate)-alt-(maleic anhydride)] on aminosilanized glass substrates were assembled and reacted in a two-step procedure, first with different mixtures of a sequence from the protein laminin, the peptide (PA22-2), and the aminopoly(ethylene oxide) (APEG) and second with the α,ω-diamine JA, to yield functionalized hydrophilic polymer films which were examined using X-ray photoelectron spectroscopy. Cell-growth experiments of embryonic hippocampal cells were performed on these surfaces, showing only cell adhesion to polymer films which were modified with the sequence from the protein laminin and the peptide (PA22-2). The cell cultures were investigated using phase contrast microscopy and immunostaining techniques together with fluorescence microscopy after 1 and 3 days, showing neuritic outgrowth of the cells after a period of 3 days.

Lipopolymers comprised of an N-isopropyl acrylamide backbone modified with lipid side chains and a disulfide moiety can be used for the preparation of thin films by chemisorption from solution and by LB-transfer as well. The resulting thin polymer layers were characterized using surface plasmon resonance, contact angle measurements, and grazing incidence FTIR spectroscopy. With both methods thin polymer films of a comparable thickness can be prepared (about 20 Å). But while chemisorption is the easier technique, LB-transfer has the advantage that a transfer at different surface areas allows an additional variation of the film thickness and the contact angle.

The reaction of poly[(1-methylvinyl isocyanate)-alt-(maleic anhydride)] (IAP) with amino-silanized glass and silicon oxide surfaces has been investigated. Different solvents and different adsorption conditions were compared to each other by FTIR spectroscopy and ellipsometry. A reactive surface containing isocyanate and anhydride groups was formed after the adsorption of the polymer. The latter can be further functionalized using different compounds bearing hydroxyl and amino groups. Mixed layers can be established by the reaction of IAP with other polymers, such as poly(ethylene glycol). Multilayers can be built up by adsorbing a second layer of IAP onto an already functionalized first layer of IAP.

This paper is concerned with long-run average cost minimization of a stochastic inventory problem with Markovian demand, fixed ordering cost, and convex surplus cost. The states of the Markov chain represent different possible states of the environment. Using a vanishing discount approach, a dynamic programming equation and the corresponding verification theorem are established. Finally, the existence of an optimal state-dependent (s, S) policy is proved.

The movement of a ribosome along the mRNA was assessed by the following experimental strategy. mRNAs were synthesized which contained a short coding sequence with at least four codons and a 32P label at one end and an oligo(C) sequence at the other end. When these mRNAs were fixed on the ribosome with tRNAs specific for the defined codons, the oligo(C) stretches were partially outside of the ribosome, whereas the labeled ends were inside the ribosome and thus protected. The overhanging oligo(C) regions were trimmed with the cytidyl-specific RNase CL3 identifying the nucleotides of the mRNAs, which emerged from the ribosome. An mRNA enters the ribosome at nucleotide 18 +/- 1, when counting starts at the first nucleotide of the P-site codon, and leaves the ribosome at nucleotide -21 +/- 2. The ribosome does not move at either side upon A-site occupation but does so at both sides simultaneously upon translocation. The results further indicate that most of the mRNA stretches downstream and upstream of the coding region are not required for the translocation reaction. It is therefore likely that the tRNAs are pulling the mRNA through the ribosome via codon-anticodon interactions in the course of translocation.

Using pulsed neutrons of 19.8 Å wavelength a quasielastic line broadening as low as 0.03 µeV (FWHM) has been observed due to Na+ diffusion in the glass Na2O·2SiO2. From the linewidths a Na+ self-diffusion coefficient of 3.1·10-8 cm2/s at 420°C was obtained in excellent agreement with the diffusion coefficient determined for the same sample batch using22Na radioactive tracers. The experimental Q dependence of the quasielasic linewidths gives a hint for deviations from a purely random walk in an ionic glass.

In the paper there is presented a special one-product inventory model with Wiener demand process, a fixed positive lead time and a (rQ)-strategy. For generai cost functions ive give a method of computation of the long run average cost. In the case of iinear cosi functions we explicitly determine the optimal strategy parameters

The measurement of radioactivity concentrations in urine samples is an important tool for monitoring possible radionuclide intakes by occupationally exposed workers, especially for radionuclides emitting alpha or beta radiation. Quality assurance requires systematic intercomparisons involving all laboratories responsible for these measurements. Such analyses were performed by the German--Swiss Radiation Protection Association. The main purpose of these measurements was the specification of criteria for the acceptance of laboratories by radiation protection authorities. This contribution presents some measurement results of Th-nat, 90 Sr, and 241 Am in urine and discusses the implications for internal dosimetry.

The sequential layer-by-layer formation of peptide-supported bimolecular lipid membranes at solid supports is described. In the first step, thiol-derivatized peptide sequences of 5 and 7 amino acids are assembled on a Au substrate. After activation of their COOH-terminus phospholipid molecules (DMPE) are covalently attached via an amid bond to form a tethered monolayer on the Au electrode. The different preparation steps are analyzed by Fourier transform IR, X-ray reflectometry, and surface plasmon spectroscopy. The latter technique is then also used to on-line monitor at the solid/solution interface the formation of a bilayer by fusion of vesicles prepared from a fluid lipid mixture with and without reconstituted proteins. The obtained thicknesses and capacitance values are compatible with the tethered bilayer model and point to an incorporation of ATPase into these membrane matrices.

Vector-borne diseases are rising in interest due to global warming, which is believed to impact on the distribution of vectors into new areas thus influencing the occurrence and epidemiology of vector-borne pathogens. Babesia canisbelongs to the Piroplasmidaeand there are three described subspecies, namely B. canis canis, B. canis rossiand B. canis vogeli. They are each transmitted by a different tick-species, Dermacentor reticulatus, Haemaphysalis leachiand Rhipicephalus sanguineus, respectively. There are also differences in the geographical distribution and pathogenicity to dogs of each subspecies. In this study, we aimed to establish a rapid and easy to perform DNA-based test using loop-mediated isothermal amplification to detect all three Babesia canissubspecies in one assay.