151 research outputs found

    Data Analytics and Optimization for Decision Support

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    Linear programming approach for solving stochastic control problem on networks with discounted transition costs

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    Секция 10. Теоретическая информатикаThe infinite horizon stochastic control problem on network with expected total discounted cost optimization criterion is studied. A linear programming approach for solving this problem on networks is developed. Moreover, a polynomial tim

    Adiabatic Pair Creation

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    We give here the proof that pair creation in a time dependent potentials is possible. It happens with probability one if the potential changes adiabatically in time and becomes overcritical, that is when an eigenvalue enters the upper spectral continuum. The potential may be assumed to be zero at large negative and positive times. The rigorous treatment of this effect has been lacking since the pioneering work of Beck, Steinwedel and Suessmann in 1963 and Gershtein and Zeldovich in 1970.Comment: 53 pages, 1 figure. Editorial changes on page 22 f

    Rational Engineering of a Flavoprotein Oxidase for Improved Direct Oxidation of Alcohols to Carboxylic Acids

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    The oxidation of alcohols to the corresponding carbonyl or carboxyl compounds represents a convenient strategy for the selective introduction of electrophilic carbon centres into carbohydrate-based starting materials. The O2-dependent oxidation of prim-alcohols by flavin-containing alcohol oxidases often yields mixtures of aldehyde and carboxylic acid, which is due to “over-oxidation” of the aldehyde hydrate intermediate. In order to directly convert alcohols into carboxylic acids, rational engineering of 5-(hydroxymethyl)furfural oxidase was performed. In an attempt to improve the binding of the aldehyde hydrate in the active site to boost aldehyde-oxidase activity, two active-site residues were exchanged for hydrogen-bond-donating and -accepting amino acids. Enhanced over-oxidation was demonstrated and Michaelis–Menten kinetics were performed to corroborate these findings

    Optical lattice quantum simulator for QED in strong external fields: spontaneous pair creation and the Sauter-Schwinger effect

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    Spontaneous creation of electron-positron pairs out of the vacuum due to a strong electric field is a spectacular manifestation of the relativistic energy-momentum relation for the Dirac fermions. This fundamental prediction of Quantum Electrodynamics (QED) has not yet been confirmed experimentally as the generation of a sufficiently strong electric field extending over a large enough space-time volume still presents a challenge. Surprisingly, distant areas of physics may help us to circumvent this difficulty. In condensed matter and solid state physics (areas commonly considered as low energy physics), one usually deals with quasi-particles instead of real electrons and positrons. Since their mass gap can often be freely tuned, it is much easier to create these light quasi-particles by an analogue of the Sauter-Schwinger effect. This motivates our proposal of a quantum simulator in which excitations of ultra-cold atoms moving in a bichromatic optical lattice represent particles and antiparticles (holes) satisfying a discretized version of the Dirac equation together with fermionic anti-commutation relations. Using the language of second quantization, we are able to construct an analogue of the spontaneous pair creation which can be realized in an (almost) table-top experiment.Comment: 21 pages, 10 figure

    Detection of Peptide-Based Nanoparticles in Blood Plasma by ELISA

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    Aims The aim of the current study was to develop a method to detect peptide-linked nanoparticles in blood plasma. Materials & Methods A convenient enzyme linked immunosorbent assay (ELISA) was developed for the detection of peptides functionalized with biotin and fluorescein groups. As a proof of principle, polymerized pentafluorophenyl methacrylate nanoparticles linked to biotin-carboxyfluorescein labeled peptides were intravenously injected in Wistar rats. Serial blood plasma samples were analyzed by ELISA and by liquid chromatography mass spectrometry (LC/MS) technology. Results The ELISA based method for the detection of FITC labeled peptides had a detection limit of 1 ng/mL. We were able to accurately measure peptides bound to pentafluorophenyl methacrylate nanoparticles in blood plasma of rats, and similar results were obtained by LC/MS. Conclusions We detected FITC-labeled peptides on pentafluorophenyl methacrylate nanoparticles after injection in vivo. This method can be extended to detect nanoparticles with different chemical compositions

    Biocatalytic Enantioselective Oxidation of Sec-Allylic Alcohols with Flavin-Dependent Oxidases

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    The oxidation of allylic alcohols is challenging to perform in a chemo- as well as stereo-selective fashion at the expense of molecular oxygen using conventional chemical protocols. Here, we report the identification of a library of flavin-dependent oxidases including variants of the berberine bridge enzyme (BBE) analogue from Arabidopsis thaliana (AtBBE15) and the 5-(hydroxymethyl)furfural oxidase (HMFO) and its variants (V465T, V465S, V465T/W466H and V367R/W466F) for the enantioselective oxidation of sec-allylic alcohols. While primary and benzylic alcohols as well as certain sugars are well known to be transformed by flavin-dependent oxidases, sec-allylic alcohols have not been studied yet except in a single report. The model substrates investigated were oxidized enantioselectively in a kinetic resolution with an E-value of up to >200. For instance HMFO V465S/T oxidized the (S)-enantiomer of (E)-oct-3-en-2-ol (1a) and (E)-4-phenylbut-3-en-2-ol with E>200 giving the remaining (R)-alcohol with ee>99% at 50% conversion. The enantioselectivity could be decreased if required by medium engineering by the addition of cosolvents (e.g. dimethyl sulfoxide).imag

    Identification of heat shock protein 32 (Hsp32) as a novel target in acute lymphoblastic leukemia

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    Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves as survival factor and potential target in Ph+ chronic myeloid leukemia. We here report that primary cells and cell lines derived from patients with acute lymphoblastic leukemia (ALL) express Hsp32 mRNA and the Hsp32 protein in a constitutive manner. Highly enriched CD34+/CD38- ALL stem cells also expressed Hsp32. Two Hsp32-targeting drugs, pegylated zinc protoporphyrine (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), induced apoptosis and growth arrest in the BCR/ABL1+ cell lines, in Ph- lymphoblastic cell lines and in primary Ph+ and Ph- ALL cells. The effects of PEG-ZnPP and SMA-ZnPP on growth of leukemic cells were dose-dependent. In Ph+ ALL, major growth-inhibitory effects of the Hsp32-targeting drugs were observed in imatinib-sensitive and imatinib-resistant cells. Hsp32-targeting drugs were found to synergize with imatinib, nilotinib, and bendamustine in producing growth inhibition and apoptosis in Ph+ ALL cells. A siRNA against Hsp32 was found to inhibit growth and survival of ALL cells and to synergize with imatinib in suppressing the growth of ALL cells. In conclusion, Hsp32 is an essential survival factor and potential new target in ALL.Sabine Cerny-Reiterer, Renata A. Meyer, Harald Herrmann, Barbara Peter, Karoline V. Gleixner, Gabriele Stefanzl, Emir Hadzijusufovic, Winfried F. Pickl, Wolfgang R. Sperr, Junia V. Melo, Hiroshi Maeda, Ulrich Jäger, Peter Valen

    Male factors determining the outcome of intracytoplasmic sperm injection with epididymal and testicular spermatozoa

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    Summary. During a period of 8 years, 1079 intracytoplasmic sperm injection (ICSI) procedures with aspirated epididymal or testicular spermatozoa were performed. Epididymal spermatozoa were used in 172 cycles and testicular spermatozoa or spermatids in 907 cycles. Multiple biopsies were obtained from at least two different locations in the testes. Retrieved spermatozoa were used after cryopreservation (frozen) or immediately after aspiration (fresh). Three hundred patients had obstructive azoospermia (OA) or ejaculation failure. In 414 cases, azoospermia was caused by impaired spermatogenesis resulting from maldescended testes, chemotherapy/radiotherapy, or by Sertoli-cellonly syndrome, genetic disorders or unknown aetiology. Transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal spermatozoa in men with OA (28% average birth rates in both cases). However, birth rates differed significantly with regard to the status of spermatogenesis. Treatment of men with nonobstructive azoospermia (NOA) resulted in a birth rate of 19% per cycle. In all patient groups, there was no difference in the birth rates achieved with fresh and cryopreserved spermatozoa. While testicular volume, follicle-stimulating hormone level and age of the male patient are no statistically significant prognostic factors, the underlying cause of azoospermia is the most important factor determining the outcome of ICSI with epididymal and testicular spermatozoa. The pregnancy rate is lower in NOA patients than in those with OA
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