Search

Today, the availability of methods for the activity-preserving and cost-efficient downstream processing of enzymes forms a major bottleneck to the use of these valuable tools in technical processes. A promising technology appears to be foam fractionation, which utilizes the adsorption of proteins at a gas–liquid interface. However, the employment of surfactants and the dependency of the applicability on individual properties of the target molecules are considerable drawbacks. Here, we demonstrate that a reversible fusion of the large, surface-active protein Ranaspumin-2 (Rsn-2) to a β-lactamase (Bla) enabled both surfactant-free formation of a stable foam and directed enrichment of the enzyme by the foaming. At the same time, Bla maintained 70% of its catalytic activity, which was in stark contrast to the enzyme without fusion to Rsn-2. Rsn-2 predominantly mediated adsorption. Comparable results were obtained after fusion to the structurally more complex penicillin G acylase (PGA) as the target enzyme. The results indicate that using a surface-active protein as a fusion tag might be the clue to the establishment of foam fractionation as a general method for enzyme downstream processing.

Background The most common complication after ileal pouch anal anastomosis in up to 50% of patients is an acute pouchitis. The majority of patients respond to antibiotic treatment. However, 10%-15% develops chronic antibiotic-dependent or refractory pouchitis which is usually hard to treat. Aim To evaluate the effectiveness of vedolizumab in patients with chronic pouchitis. Methods Patients with chronic antibiotic-dependent or refractory pouchitis were treated with vedolizumab (300 mg at week 0, 2, 6 and 10) in 10 IBD centres and retrospectively registered. Data were recorded until week 14 of vedolizumab treatment. In total 20 patients (12 male, median age 43 years) were included for analysis. The effectiveness was measured using the Oresland Score (OS) at week 2, 6, 10 and 14 and the pouch disease activity index (PDAI) at week 0 and 14. Results The mean OS declined from 6.8 (range 2-12) to 3.4 (range 0-11). Concordantly, the mean PDAI after 14 weeks of treatment dropped from 10 (range 5-18) to 3 (range 0-10). Only three patients reported moderate side effects. No serious side effects were recorded. In addition, symptomatic co-medication such as loperamide and tincture of opium could be terminated in 8 out of 12 patients as well as antibiotic treatment could be stopped in 17 out of 19 patients. Conclusion Our data indicate that vedolizumab could be an option in the treatment of patients with chronic, antibiotic-dependent or refractory pouchitis.

Purpose Avoiding measurement variability from 18F phantom preparation by using 68Ge/68Ga phantoms for the determination of 18F recovery curves (RC) in clinical quality assurance measurements and for PET/CT site qualification in multicentre clinical trials. Methods RCs were obtained from PET/CT measurements of seven differently sized phantom spheres filled either with 18F or with 68Ga. RCs for the respective other isotope were then determined by two different methods: In the first method, images were convolved with positron range transconvolution functions derived from positron annihilation distributions found in literature. This method generated re-casted images matching images using the respective other isotope. In the second method, the PET/CT system's isotope independent (intrinsic) point spread function was determined from said phantom measurements and convolved with numerical representations simulating hot spheres filled with the respective other isotope. These simulations included the isotope specific positron annihilation distributions. Recovered activity concentrations were compared between re-casted images, simulated images and the originally acquired images. Results 18F and 68Ga recovery was successfully determined from image acquisitions of the respective opposite isotope as well as from the simulations. 68Ga RCs derived from 18F data had a normalized root-mean-square deviation (NRMSD) from real 68Ga measurements of 0.019 % when using the first method and of 0.008 % when using the second method. 18F RCs derived from 68Ga data had a NRMSD from real 18F measurements of 0.036 % when using the first method and of 0.038 % when using the second method. Conclusions Applying the principles of transconvolution, 18F RCs can be recalculated from 68Ga phantom measurements with excellent accuracy. The maximal additionally introduced error was below 0.4% of the error currently accepted for RCs in the site qualification of multicentre clinical trials by the EARL program of the European Association of Nuclear Medicine (EANM). Therefore, our methods legitimately allow for the use of long-lived solid state 68Ge/68Ga phantoms instead of manually prepared 18F phantoms to characterize comparability of 18F measurements across different imaging sites or of longitudinal18F measurements at a single PET/CT system. This article is protected by copyright. All rights reserved.

Objective Elevated levels of cardiac troponin, and especially their relative changes over time, indicate acute myocardial injury. They are also frequently observed after acute ischemic stroke (AIS), indicating poor functional outcome and increased mortality. However, recent evidence showed that, in most AIS patients, myocardial injury is not caused by coronary ischemia. Instead, stroke lesion location has been suggested to precipitate myocardial injury. Methods Voxel-based lesion-symptom mapping (VLSM) was used in 299 patients who had a magnetic resonance imaging–confirmed acute ischemic stroke within the anterior circulation and a high-sensitivity cardiac troponin T (hs-cTnT) acquired on the day of admission. Of these, 228 had a second troponin measurement during the acute phase. The absolute hs-cTnT levels above the 99th percentile of a healthy reference population (≥14ng/l) as well as their relative temporal changes were used as continuous variables of interest in the VLSM model, including a multiple regression analysis adjusted for confounding variables. Results The anterior insular cortex of the right hemisphere, in particular its dorsal subregion, was significantly associated with the relative temporal changes of hs-cTnT (p

PURPOSE A PET/CT system's imaging capabilities are best described by its point spread function (PSF) in the spatial domain or equivalently by its modulation transfer function (MTF) in the spatial frequency domain. Knowing PSFs or MTFs is a prerequisite for many numerical methods attempting to improve resolution and to reduce the partial volume effect. In PET/CT, the observed PSF is a convolution of the system's intrinsic imaging capabilities including image reconstruction (PSF0) and the positron range function (PRF) of the imaged β(+) emitting isotope. A PRF describes the non-Gaussian distribution of β(+) annihilation events around a hypothetical point source. The main aim was to introduce a new method for determining a PET/CT system's intrinsic MTF (MTF0) from phantom measurements of hot spheres independently of the β(+) emitting isotope used for image acquisition. Secondary aim was to examine non-Gaussian and nonlinear MTFs of a modern iterative reconstruction algorithm. METHODS PET/CT images of seven phantom spheres with volumes ranging from 0.25 to 16 ml and filled either with (18)F or with (68)Ga were acquired and reconstructed using filtered back projection (FBP). MTFs were modeled with linear splines. The spline fit iteratively minimized the mean squared error between the acquired PET/CT image and a convolution of the thereof derived PSF with a numerical representation of the imaged hot phantom sphere. For determining MTF0, the numerical sphere representations were convolved with a PRF, simulating a fill with either (18)F or (68)Ga. The MTFs determined by this so-called MTF fit method were compared with MTFs derived from point source measurements and also compared with MTFs derived with a previously published PSF fit method. The MTF fit method was additionally applied to images reconstructed by a vendor iterative algorithm with PSF recovery (Siemens TrueX). RESULTS The MTF fit method was able to determine (18)F and (68)Ga dependent MTFs and MTF0 from FBP reconstructed images. Root-mean-square deviation between fit determined MTFs and point source determined MTFs ranged from 0.023 to 0.039. MTFs from Siemens TrueX reconstructions varied with size of the imaged sphere. CONCLUSIONS MTF0 can be determined regardless of the imaged isotope, when using existing PRF models for the MTF fit method presented. The method proves that modern iterative PET/CT reconstruction algorithms have nonlinear imaging properties. This behaviour is not accessible by point source measurements. MTFs resulting from these clinically applied algorithms need to be estimated from objects of similar geometry to those intended for clinical imaging.

In the present paper, the force-fit connection of discrete ceramic components by means of geometrically interlocking surfaces is studied. These surfaces possess a concavo-convex topology permitting assembly of structures in which each individual element is kinematically locked by its neighbors. Such structures have a tuneable bending stiffness, allow for large deformations and are tolerant to missing or destroyed elements. These properties of topologically interlocked structures make them particularly attractive in construction with brittle materials. The elements used were produced by freeze gelation of ceramic slurries, leading to near net shape with the coefficient of shrinkage below 3%. It is shown that planar assemblies of interlocked ceramic elements can withstand flexural deflections up to a ten-fold of those a solid plate from the same material can sustain. The response of these structures to concentrated load can be divided into an elastic and a quasi-plastic, i.e., irreversible, part. After the point of maximum load, the interlocked structures investigated were still able to withstand further deformation, whereas solid plates showed brittle failure.

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

The copolymerisation behaviour of diallylmaleate (DAM) with methyl methacrylate (MMA), N-phenylmaleimide (NPI), and styrene (S) in radical polymerisation was studied under the aspect of interaction of monomers with high and low electron density vinyl groups. The system DAM/S showed some indications for interaction. Generally, the strong control of degradative chain transfer could be recognised in polymerisation. A huge increase of the molecular mass is observed at low parts of DAM in the monomer composition.

Symptoms of angina pectoris and transient ST-segment depression are most commonly used to evidence acute myocardial ischemia during exercise testing. However, the diagnostic accuracy of either or both criteria in relation to clinical characteristics and the patient's exercise response has been a subject of controversy. The prevalence and severity of symptoms of angina pectoris and/or ST-segment depression were studied prospectively in 147 consecutive patients with a history of daily angina pectoris, scintigraphic evidence of exercise-induced myocardial ischemia, and coronary artery stenosis >75%. Logistic regression analysis was applied to determine absence of any or both criteria by the clinical characteristics or exercise response of the patient. During exercise testing, ST-segment response failed to prove scintigraphically evidenced myocardial ischemia in 14/147 patients (10%) and 35/147 patients (24%) when ST-segment depression ≥0.1 in either ≥1 or ≥2 ECG leads was chosen. Symptoms of angina pectoris were found to be absent in 69/147 patients (47%). Only 58 patients (40%) suffered from angina and met the ECG criterion at the time of scintigraphic myocardial ischemia. Absence of ST-segment depression was best predicted by clinical variables such as large myocardial infarction (increase: 2.6 times, p = 0.007), number of stenoses ≥2 (2.0 times, p = 0.023), and presence of diabetes mellitus (4.3 times, p = 0.035). Painless myocardial ischemia was only determined by blood response to exercising. Thus, a double product > 23 increased the risk of painless myocardial ischemia by 1.5 times (p = 0.017). In multivariate analysis, only blood pressure response, infarction size, and the number of diseased vessels were found to be independent predictors of the absence of angina pectoris or ST-segment depression during myocardial ischemia.

Die als Folge einer Behandlung mit Natronlauge im Konzentrationsbereich von 0–50% NaOH eintretenden Veranderungen des Ordnungszustandes verschiedener Cellulosefasern (Holzzellstoffe und Baumwollinters) wurden infrarotspektroskopisch und rontgenographisch verfolgt. Die Bestimmung eines IR-Index als Relation der Peakflachen im Wellenzahlenbereich von 1370 und 670 cm−1 gestatteten eine mit geringem Aufwand durchzufuhrende Bestimmung insbesondere der im Gebiet der Natronlaugenkonzentrationen von 7.5–15%iger Lauge signifikant abfallenden Kristallinitat. Weitaus aufwendigere rontgenographische Messungen des Kristallinitatsindex bestatigen die infrarotspektroskopisch erhaltenenen Befunde. Es ergibt sich die Moglichkeit, anhand gewisser Unterschiede im Verlauf der IR-Indexkurven Schlusse in bezug auf die Aktivierungsfahigkeit einzelner Faserproben zu ziehen.

Purpose: Positron emission tomography (PET)/computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET/CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET/CT in the context of multicenter trials. Methods: To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET/CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculatedmore » by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET/CT systems, a dedicated solid-state phantom incorporating {sup 68}Ge/{sup 68}Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hann's apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET/CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. Results: The proposed Transconvolution method matched different PET/CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. Conclusions: By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.« less

Es wurde der Versuch unternommen, durch Umsetzung von Zellstoffen mit Glycidyltrimethylammoniumchlorid im Losungsmittelsystem Dimethylacetamid/Lithiumchlorid kationische Cellulosederivate mit moglichst hohen Substitutionsgraden zu erhalten. Hierzu wurden Temperaturabhangigkeit, Reaktionsdauer und Molverhaltnis der Reaktanden untersucht. Als optimal erwies sich eine Reaktionsdauer von 8 h bei einer Reaktionstemperatur von 70°C. Der Cellulosegehalt in Losung und das Molverhaltnis der Reaktanden mussen dem verwendeten Zellstoff angepast werden. An attempt was made to obtain cationic cellulose derivatives of highest possible degrees of substitution by treating dissolving grade pulps under homogeneous conditions with glycidyltrimethylammonium chloride in the solvent system dimethylacetamide/lithiumchloride. The influence of temperature, reaction time and molar ratio of the reagents was examined. A reaction time of 8 h and a temperature of 70°C have been found to be optimal. The cellulose content in solution and the molar ratio of the reagents have to be adapted to the used pulp.

An uber 20 Derivaten von N'-methylierten Saurehydraziden (1-Methylsemicarbaziden, 3-Methyl-carbazinsaureestern, N'-Methylcarbonsaurehydraziden, N'-Methylsulfonsaurehydraziden) wird die Anwendungsbreite der zu entsprechend acylierten Hexahydro-1,2,4,5-tetrazinen fuhrenden Oxidation mit Blei(IV)-acetat untersucht; als reaktive Zwischenprodukte werden 1,3-dipolare N'-acylierte Carbenium-iminium-N-imide diskutiert. Oxidative Cyclization of N'-Methylhydrazides with Lead Tetraacetate Acylated hexahydro-1,2,4,5-tetrazines are obtained from N'-methylhydrazides by oxidation with lead tetraacetate. The range of application of this reaction was investigated using more than 20 hydrazides. 1,3-Dipolar species of type 3 are discussed as intermediates.