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1.
Textbook procedures require the use of individual aptamers enriched in SELEX libraries which are subsequently chemically synthesized after their biochemical characterization. Here we show that this reduction of the available sequence space of large libraries and thus the diversity of binding molecules reduces the labelling efficiency and fidelity of selected single aptamers towards different strains of the human pathogen Pseudomonas aeruginosa compared to a polyclonal aptamer library enriched by a whole-cell-SELEX involving fluorescent aptamers. The library outperformed single aptamers in reliable and specific targeting of different clinically relevant strains, allowed to inhibit virulence associated cellular functions and identification of bound cell surface targets by aptamer based affinity purification and mass spectrometry. The stunning ease of this FluCell-SELEX and the convincing performance of the P. aeruginosa specific library may pave the way towards generally new and efficient diagnostic techniques based on polyclonal aptamer libraries not only in clinical microbiology.  相似文献   
2.
3.
The coupled task problem is to schedule jobs on a single machine where each job consists of two subtasks and where the second subtask has to be started after a given time interval with respect to the first one. The problem has several applications and is NP-hard. In this paper we present a branch-and-bound algorithm for this problem and compare its performance with four integer programming models.  相似文献   
4.
Gamma ray measurements were carried out along two parallel lines close to each of the hot springs using a RS 125 spectrometer to find the concentration (ppm) of U, Th, and K at Polile Tshisa, Aliwal North, and Badfontein hot springs. The RS 125 spectrometer is auto-stabilized on the naturally occurring U, Th, and K, and provides concentrations (ppm) of the radioelements. The results show that the concentration of thorium is higher, and is below the world average hazardous threshold of 7.4 ppm. Thorium is related to the occurrence of monazite seen at the scanning electron microscope. Higher ratios of U/K are indicative of an increase of uranium relative to potassium. Binary diagrams (Th–U, KU, and K–Th) do not show a clear best fit except at Polile Tshisa hot spring where thorium shows a quasi positive correlation to potassium. In general, it can be concluded that the concentrations of these three radioelements are quite low, acceptable for groundwater, and could be hazardous to the health of humans and animals if exposed to long time radiations.  相似文献   
5.
1,1,1,3,3,3‐hexafluoro‐propan‐2‐ol aggregates preferentially into an achiral dimer of achiral monomers, but the trimer is found to prefer three metastable chiral monomer units arranged into a strained OH???O hydrogen‐bonded ring, which is reinforced by secondary CH???FC interactions. This is shown by a combination of infrared, microwave, and Raman spectroscopy in supersonic jet expansions and supported by high‐level quantum chemical calculations. It involves an activation of the monomers by >15 kJ mol?1, clearly driven by the much stronger hydrogen‐bond interaction available to the gauche and even more to the cis monomer units.  相似文献   
6.
A new crystalline form of αβ‐d ‐lactose prepared by oven drying a concentrated aqueous solution of d ‐lactose is a lesson in the power of observation and the rigorous analysis of powder samples.  相似文献   
7.
LiCoPO4-coated disordered carbon nanofibers (CNFs/LiCoPO4) were obtained by a sol–gel method, using triethyl phosphite or triethyl phosphate as the phosphorous source. The crystal structure of the products was analyzed by X-ray powder diffraction, while morphology was studied using scanning electron microscopy, transmission electron microscopy, Auger electron spectroscopy and X-ray photoelectron spectroscopy. Optimal synthesis conditions for the CNFs/LiCoPO4 in light of the best electrochemical performance are discussed. The best discharge capacity 105 mAh/g (or ca. 63% of the theoretical capacity) shows the material with 40% CNFs/LiCoPO4 and addition coating by carbon black. This composition has a best purity of active materials and point coverage of CNFs. The X-ray photoelectron C1s spectra of the CNFs surface without and with sputter erosion show enhancement of C–O bonds at the fiber surface, which does not influence significantly electrochemical behavior of the composite materials.  相似文献   
8.
Complexes of the benzenium ion (C(6)H(7)(+)) with N(2) or CO(2) have been studied by explicitly correlated coupled cluster theory at the CCSD(T)-F12x (x = a, b) level [T. B. Adler et al., J. Chem. Phys. 127, 221106 (2007)] and the double-hybrid density functional B2PLYP-D [T. Schwabe and S. Grimme, Phys. Chem. Chem. Phys. 9, 3397 (2007)]. Improved harmonic vibrational wavenumbers for C(6)H(7)(+) have been obtained by CCSD(T?)-F12a calculations with the VTZ-F12 basis set. Combining them with previous B2PLYP-D anharmonic contributions we arrive at anharmonic wavenumbers which are in excellent agreement with recent experimental data from p-H(2) matrix isolation IR spectroscopy [M. Bahou et al., J. Chem. Phys. 136, 154304 (2012)]. The energetically most favourable conformer of C(6)H(7)(+)·N(2) shows a π-bonded structure similar to C(6)H(7)(+)·Rg (Rg = Ne, Ar) [P. Botschwina and R. Oswald, J. Phys. Chem. A 115, 13664 (2011)] with D(e) ≈ 870 cm(-1). For C(6)H(7)(+)·CO(2), a slightly lower energy is calculated for a conformer with the CO(2) ligand lying in the ring-plane of the C(6)H(7)(+) moiety (D(e) ≈ 1508 cm(-1)). It may be discriminated from other conformers through a strong band predicted at 1218 cm(-1), red-shifted by 21 cm(-1) from the corresponding band of free C(6)H(7)(+).  相似文献   
9.

Background

Antisense oligonucleotide (AON)-mediated exon skipping is a powerful tool to manipulate gene expression. In the present study we investigated the potential of exon skipping by local injection in the central nucleus of the amygdala (CeA) of the mouse brain. As proof of principle we targeted the splicing of steroid receptor coactivator-1 (SRC-1), a protein involved in nuclear receptor function. This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon.

Methods

For proof of principle of feasibility, we used immunofluorescent stainings to study uptake by different cell types, translocation to the nucleus and potential immunostimulatory effects at different time points after a local injection in the CeA of the mouse brain of a control AON targeting human dystrophin with no targets in the murine brain. To evaluate efficacy we designed an AON targeting the SRC-1e-specific exon and with qPCR analysis we measured the expression ratio of the two splice variants.

Results

We found that AONs were taken up by corticotropin releasing hormone expressing neurons and other cells in the CeA, and translocated into the cell nucleus. Immune responses after AON injection were comparable to those after sterile saline injection. A successful shift of the naturally occurring SRC-1a:SRC-1e expression ratio in favor of SRC-1a was observed, without changes in total SRC-1 expression.

Conclusions

We provide a proof of concept for local neuropharmacological use of exon skipping by manipulating the expression ratio of the two splice variants of SRC-1, which may be used to study nuclear receptor function in specific brain circuits. We established that exon skipping after local injection in the brain is a versatile and useful tool for the manipulation of splice variants for numerous genes that are relevant for brain function.  相似文献   
10.
ABSTRACT

An analytical computer simulation procedure for dynamic modeling of low-contact-ratio spur gear systems is presented. The procedure computes the gear static transmission error and uses a Fast Fourier Transform (FFT) to generate its frequency spectrum at various tooth profile modifications. The dynamic loading response of an unmodified (perfect involut) gear pair is compared with that of gears with profile modifications. Correlations are found between several profile modifications and the resulting dynamic loads. An effective error, obtained from frequency domain anal  相似文献   
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