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History of political thought
(2012)
Schröder, Peter ; Asbach, Olaf ; Breckman, Warren ; Bourke, Richard ; Busen, Andreas ; D'Aprile, Iwan-Michelangelo ; Hunter, Ian
Machumi, Francis ; Yenesew, Abiy ; Midiwo, Jacob O. ; Heydenreich, Matthias ; Kleinpeter, Erich ; Tekwani, Babu L. ; Khan, Shabana I. ; Walker, Larry A. ; Muhammad, Ilias
The CH2Cl2-MeOH (1:1) extract of the aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, showed activity against chloroquine sensitive D6 (IC50 9.7 mu g/mL) and chloroquine resistant W2 (IC50 15.0 mu g/mL) strains of Plasmodium falciparum. Seventeen secondary metabolites were isolated from the extract through conventional chromatographic techniques and identified using various spectroscopic methods. The compounds were evaluated for their in vitro antiplasmodial, antileishmanial and anticancer activities revealing activity of four carvotacetone derivatives, namely 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) 3,7-dihydroxy-5-tigloyloxycarvotacetone (2), 3-acetoxy-5,7-dihydroxycarvotacetone (3) and 3,5,7-trihydroxycarvotacetone (4); with antiplasmodial IC50 values of 1.40, 0.79, 0.60 and 3.40 mu g/mL, respectively, against chloroquine sensitive D6 strains of P. falciparum; antiplasmodial activity of IC50 2.00, 0.90, 0.68 and 2.80 mu g/mL respectively, against chloroquine resistant W2 strains of P. falciparum, antileishmanial IC50, values of 0.70, 3.00, 0.70 and 17.00 mu g/mL, respectively, against the parasite L. donovanii promastigotes, and anticancer activity against human SK-MEL, KB, BT-549 and SK-OV-3 tumor cells, with IC50 values between <1.1 - 5.3 mu g/mL, for 1-3. In addition, cytotoxic effects of the active compounds were evaluated against monkey kidney fibroblasts (VERO) and pig kidney epithelial cells (LLC-PK11). The structures of carvotacetone derivatives were determined by ID and 2D NMR spectroscopy; the absolute stereochemical configuration of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (I) was determined as 3R, 4R, 5S by circular dichroism, specific rotation, H-1 NMR and 2D NMR ROESY and NOESY experiments.
Induli, Martha ; Cheloti, Michael ; Wasuna, Antonina ; Wekesa, Ingrid ; Wanjohi, John M. ; Byamukama, Robert ; Heydenrich, Matthias ; Makayoto, Moses ; Yenesew, Abiy
Two new naphthoquinones, 5-hydroxy-3,6-dimethoxy-2-methylnaphthalene-1,4-dione and 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione, were isolated from the roots of Aloe secundiflora together with the known compounds chrysophanol, helminthosporin, isoxanthorin, ancistroquinone C, aloesaponarins I and II, aloesaponols I and II, laccaic acid D methyl ester and asphodelin. The structures were elucidated based on spectroscopic evidence. This appears to be the first report on the occurrence of naphthoquinones in the genus Aloe. Aloesaponarin I and 5-hydroxy-3,6-dimethoxy-2-methylnaphthalene-1,4-dione showed anti-bacterial activity against Mycobacterium tuberculosis with MIC values of 21-23 mu g/mL in the Microplate Alamar Blue Assay (MABA) and Low Oxygen Recovery Assay (LORA); 5-hydroxy-3,6-dimethoxy-2-methylnaphthalene-1,4-dione also showed cytotoxicity against the Vero cell line (IC50 = 10.2 mu g/mL).
From the stem bark of Platycelphium voense (Leguminosae) four new isoflavanones were isolated and characterized as (S)-5,7-dihydroxy-2 ',4 '-dimethoxy-3 '-(3 ''-methylbut-2 ''-enyl)-isoflavanone (trivial name platyisoflavanone A), (+)-5,7,2 '-trihydroxy-4 '-methoxy-3 '-(3 ''-methylbut-2 ''-enyl)-isoflavanone (platyisoflavanone B), 5,7-dihydroxy-4 '-methoxy-2 ''-(2 '''-hydroxyisopropyl)-dihydrofurano-[4 '',5 '':3 ',2 ']-isoflavanone (platyisoflavanone C) and 5,7,2 ',3 ''-tetrahydroxy-2 '',2 ''-dimethyldihydropyrano-[5 '',6 '':3 ',4 ']-isoflavanone (platyisoflavanone D). In addition, the known isoflavanones, sophoraisoflavanone A and glyasperin F; the isoflavone, formononetin; two flavones, kumatakenin and isokaempferide; as well as two triterpenes, betulin and beta-amyrin were identified. The structures were elucidated on the basis of spectroscopic evidence. Platyisoflavanone A showed antibacterial activity against Mycobacterium tuberculosis in the microplate alamar blue assay (MABA) with MIC = 23.7 mu M, but also showed cytotoxicity (IC50 = 21.1 mu M) in the vero cell test.
Virtual 3D city models serve as an effective medium with manifold applications in geoinformation systems and services. To date, most 3D city models are visualized using photorealistic graphics. But an effective communication of geoinformation significantly depends on how important information is designed and cognitively processed in the given application context. One possibility to visually emphasize important information is based on non-photorealistic rendering, which comprehends artistic depiction styles and is characterized by its expressiveness and communication aspects. However, a direct application of non-photorealistic rendering techniques primarily results in monotonic visualization that lacks cartographic design aspects. In this work, we present concepts for cartography-oriented visualization of virtual 3D city models. These are based on coupling non-photorealistic rendering techniques and semantics-based information for a user, context, and media-dependent representation of thematic information. This work highlights challenges for cartography-oriented visualization of 3D geovirtual environments, presents stylization techniques and discusses their applications and ideas for a standardized visualization. In particular, the presented concepts enable a real-time and dynamic visualization of thematic geoinformation.
Hybrid terrains are a convenient approach for the representation of digital terrain models, integrating heterogeneous data from different sources. In this article, we present a general, efficient scheme for achieving interactive level-of-detail rendering of hybrid terrain models, without the need for a costly preprocessing or resampling of the original data. The presented method works with hybrid digital terrains combining regular grid data and local high-resolution triangulated irregular networks. Since grid and triangulated irregular network data may belong to different datasets, a straightforward combination of both geometries would lead to meshes with holes and overlapping triangles. Our method generates a single multiresolution model integrating the different parts in a coherent way, by performing an adaptive tessellation of the region between their boundaries. Hence, our solution is one of the few existing approaches for integrating different multiresolution algorithms within the same terrain model, achieving a simple interactive rendering of complex hybrid terrains.
Virtual 3D city models play an important role in the communication of complex geospatial information in a growing number of applications, such as urban planning, navigation, tourist information, and disaster management. In general, homogeneous graphic styles are used for visualization. For instance, photorealism is suitable for detailed presentations, and non-photorealism or abstract stylization is used to facilitate guidance of a viewer's gaze to prioritized information. However, to adapt visualization to different contexts and contents and to support saliency-guided visualization based on user interaction or dynamically changing thematic information, a combination of different graphic styles is necessary. Design and implementation of such combined graphic styles pose a number of challenges, specifically from the perspective of real-time 3D visualization. In this paper, the authors present a concept and an implementation of a system that enables different presentation styles, their seamless integration within a single view, and parametrized transitions between them, which are defined according to tasks, camera view, and image resolution. The paper outlines potential usage scenarios and application fields together with a performance evaluation of the implementation.
Mayer, Frank ; Bonaventura, Klaus ; Cassel, Michael ; Müller, Steffen ; Weber, Josefine ; Scharhag-Rosenberger, Friederike ; Carlsohn, Anja ; Baur, Heiner ; Scharhag, Jürgen
Background Preparticipation examinations (PPE) are frequently used to evaluate eligibility for competitive sports in adolescent athletes. Nevertheless, the effectiveness of these examinations is under debate since costs are high and its validity is discussed controversial.
Purpose To analyse medical findings and consequences in adolescent athletes prior to admission to a sports school.
Methods In 733 adolescent athletes (318 girls, 415 boys, age 12.3+/-0.4, 16 sports disciplines), history and clinical examination (musculoskeletal, cardiovascular, general medicine) was performed to evaluate eligibility. PPE was completed by determination of blood parameters, ECG at rest and during ergometry, echocardiography and x-rays and ultrasonography if indicated. Eligibility was either approved or rated with restriction. Recommendations for therapy and/or prevention were given to the athletes and their parents.
Results Historical (h) and clinical (c) findings (eg, pain, verified pathologies) were more frequent regarding the musculoskeletal system (h: 120, 16.4%; c: 247, 33.7%) compared to cardiovascular (h: 9, 1.2%; c: 23, 3.1%) or general medicine findings (h: 116, 15.8%; c: 71, 9.7%). ECG at rest was moderately abnormal in 46 (6.3%) and severely abnormal in 25 athletes (3.4%). Exercise ECG was suspicious in 25 athletes (3.4%). Relevant echocardiographic abnormalities were found in 17 athletes (2.3%). In 52 of 358 cases (14.5%), x-rays led to diagnosis (eg, Spondylolisthesis). Eligibility was temporarily restricted in 41 athletes (5.6%). Three athletes (0.4%) had to be excluded from competitive sports. Therapy (eg, physiotherapy, medication) and/or prevention (sensorimotor training, vaccination) recommendations were deduced due to musculoskeletal (t:n = 76,10.3%; p:n = 71,9.8%) and general medicine findings (t:n = 80, 10.9%; p:n = 104, 14.1%).
Conclusion Eligibility for competitive sports is restricted in only 5.5% of adolescent athletes at age 12. Eligibility refusals are rare. However, recommendations for therapy and prevention are frequent, mainly regarding the musculoskeletal system. In spite of time and cost consumption, adolescent preparticipation before entering a career in high-performance sports is supported.
Background: To determine the general appearance of normal axillary lymph nodes (LNs) in real-time tissue sonoelastography and to explore the method's potential value in the prediction of LN metastases.
Methods: Axillary LNs in healthy probands (n=165) and metastatic LNs in breast cancer patients (n=15) were examined with palpation, B-mode ultrasound, Doppler and sonoelastography (assessment of the elasticity of the cortex and the medulla). The elasticity distributions were compared and sensitivity (SE) and specificity (SP) were calculated. In an exploratory analysis, positive and negative predictive values (PPV, NPV) were calculated based upon the estimated prevalence of LN metastases in different risk groups.
Results: In the elastogram, the LN cortex was significantly harder than the medulla in both healthy (p=0.004) and metastatic LNs (p=0.005). Comparing healthy and metastatic LNs, there was no difference in the elasticity distribution of the medulla (p=0.281), but we found a significantly harder cortex in metastatic LNs (p=0.006). The SE of clinical examination, B-mode ultrasound, Doppler ultrasound and sonoelastography was revealed to be 13.3%, 40.0%, 14.3% and 60.0%, respectively, and SP was 88.4%, 96.8%, 95.6% and 79.6%, respectively. The highest SE was achieved by the disjunctive combination of B-mode and elastographic features (cortex >3mm in B-mode or blue cortex in the elastogram, SE=73.3%). The highest SP was achieved by the conjunctive combination of B-mode ultrasound and elastography (cortex >3mm in B-mode and blue cortex in the elastogram, SP=99.3%).
Conclusions: Sonoelastography is a feasible method to visualize the elasticity distribution of LNs. Moreover, sonoelastography is capable of detecting elasticity differences between the cortex and medulla, and between metastatic and healthy LNs. Therefore, sonoelastography yields additional information about axillary LN status and can improve the PPV, although this method is still experimental.
Intra- and interrater variability of sonographic investigations of patella and achilles tendons
(2012)
Background: Clinical examinations of tendon disorders routinely include ultrasound examinations, despite the fact that availability of data concerning validity criteria of these measurements are limited. The present study therefore aims to evaluate the reliability of measurements of Achilles- and Patella tendon diameter and in the detection of structural adaptations.
Materials and Methods: In 14 healthy, recreationally active subjects both asymptomatic Achilles (AT) and patella tendons (PT) were measured twice by two examiners in a test-retest design. Besides the detection of anteroposterior (a.p.-) and mediolateral (m.l.-) diameters, areas of hypoechogenicity and neovascularisation were registered. Data were analysed descriptively with calculation of test-retest variability (TRV), intraclass-correlation coefficient (ICC) and Bland and Altman's plots with bias and 95% limits of agreement (LOA).
Results: Intra- and interrater differences of AT- and PT-a.p.-diameter varied from 0.2 - 1.2 mm, those of AT- and PT-m.l-diameter from 0.7-5.1 mm. Areas of hypoechogenicity were visible in 24% of the tendons, while 15% showed neovascularisations. Intrarater AT-a.p.-diameters showed sparse deviations (TRV 4.5-7.4%; ICC 0.60-0.84; bias -0.05-0.07 mm; LOA-0.6-0.5 to -1.1 - 1.0 mm), while interrater AT- and PT-m.l.-diameters were highly variable (TRV 13.7-19.7%; ICC 0.11-0.20; bias -1.4-4.3 mm; LOA-5.5-2.7 to -10.5 - 1.9 mm).
Conclusion: Our results suggest that the measurement of AT- and PT-a.p.-diameters is a reliable parameter. In contrast, reproducibility of AT- and PT-m.l.-diameters is questionable. The study corroborates the presence of hypoechogenicity and neovascularisation in asymptomatic tendons.
Wojcinski, Sebastian ; Cassel, Michael ; Farrokh, Andre ; Soliman, Amr A. ; Hille, Ursula ; Schmidt, Werner ; Degenhardt, Friedrich ; Hillemanns, Peter
Objectives-The purpose of this study was to determine the dependence of breast tissue elasticity on the menstrual cycle of healthy volunteers by means of real-time sonoelastography.
Methods-Twenty-two healthy volunteers (aged 18-33 years) were examined once weekly during two consecutive menstrual cycles using sonoelastography. Group 1 (n = 10) was not taking hormonal medication; group 2 (n = 12) was taking oral contraceptives.
Results-The breast parenchyma appeared softer than the dermis and harder than the adipose tissue, and elasticity varied over the menstrual cycle and between groups. Group 1 (no hormone intake) showed continuously increasing elasticity with relatively soft breast parenchyma in the menstrual and follicular phases and harder parenchyma in the luteal phase (P = .012). Group 2 (oral contraceptives) showed no statistically significant changes in breast parenchymal elasticity according to sonoelastography. The parenchyma was generally softer in group 1 compared with group 2 throughout the menstrual cycle (P = .033). The dermis, the subcutaneous adipose tissue, and the pectoralis major muscle showed no changes in elasticity. Comparison of measurements made during the first and the second menstrual cycles showed similar patterns of elasticity in both groups.
Conclusions-Sonoelastography is a reproducible method that can be used to determine the dependence of breast parenchyma elasticity on the menstrual cycle and on the intake of hormonal contraceptives.
Neuromuscular activity of the lower leg is dependent on the task performed, speed of movement and gender. Whether training volume influences neuromuscular activity is not known. The EMG of physically active persons differing in running mileage was analysed to investigate this. 55 volunteers were allocated to a low (LM: < 30 km), intermediate (IM: > 30 km & < 45 km) or high mileage (HM: > 45 km) group according to their weekly running volume. Neuromuscular activity of the lower leg was measured during running (3.33 m.s(-1)). Mean amplitude values for preactivation, weight acceptance and push-off were calculated and normalised to the mean activity of the entire gait cycle. Higher activity in the gastrocnemius group was observed in weight acceptance in LM compared to IM (+30%) and HM (+25%) but lower activity was present in the push-off for LM compared to IM and HM. For the peroneal muscle, differences were present in the push-off where HM showed increased activity compared to IM (+24%) and LM (+60%). The tibial muscle revealed slightly lower activity during preactivation for the high mileage runners. Neuromuscular activity differs during stance between the high and intermediate group compared to low mileage runners. Slight adaptations in neuromuscular activation indicate a more target-oriented activation strategy possibly due to repetitive training in runners with higher weekly mileage.
Ultrasound evaluation of the patellar tendon cross-sectional area and its relation to maximum force
(2012)
Dorenkamp, Marc ; Bonaventura, Klaus ; Sohns, Christian ; Becker, Christoph R. ; Leber, Alexander W.
Aims The study aims to determine the direct costs and comparative cost-effectiveness of latest-generation dual-source computed tomography (DSCT) and invasive coronary angiography for diagnosing coronary artery disease (CAD) in patients suspected of having this disease.
Methods The study was based on a previously elaborated cohort with an intermediate pretest likelihood for CAD and on complementary clinical data. Cost calculations were based on a detailed analysis of direct costs, and generally accepted accounting principles were applied. Based on Bayes' theorem, a mathematical model was used to compare the cost-effectiveness of both diagnostic approaches. Total costs included direct costs, induced costs and costs of complications. Effectiveness was defined as the ability of a diagnostic test to accurately identify a patient with CAD.
Results Direct costs amounted to (sic)98.60 for DSCT and to (sic)317.75 for invasive coronary angiography. Analysis of model calculations indicated that cost-effectiveness grew hyperbolically with increasing prevalence of CAD. Given the prevalence of CAD in the study cohort (24%), DSCT was found to be more cost-effective than invasive coronary angiography ((sic)970 vs (sic)1354 for one patient correctly diagnosed as having CAD). At a disease prevalence of 49%, DSCT and invasive angiography were equally effective with costs of (sic)633. Above a threshold value of disease prevalence of 55%, proceeding directly to invasive coronary angiography was more cost-effective than DSCT.
Conclusions With proper patient selection and consideration of disease prevalence, DSCT coronary angiography is cost-effective for diagnosing CAD in patients with an intermediate pretest likelihood for it. However, the range of eligible patients may be smaller than previously reported.
Kössl, Manfred ; Voss, Cornelia ; Mora, Emanuel C. ; Macias, Silvio ; Föller, Elisabeth ; Vater, Marianne
Neuronal computation of object distance from echo delay is an essential task that echolocating bats must master for spatial orientation and the capture of prey. In the dorsal auditory cortex of bats, neurons specifically respond to combinations of short frequency-modulated components of emitted call and delayed echo. These delay-tuned neurons are thought to serve in target range calculation. It is unknown whether neuronal correlates of active space perception are established by experience-dependent plasticity or by innate mechanisms. Here we demonstrate that in the first postnatal week, before onset of echolocation and flight, dorsal auditory cortex already contains functional circuits that calculate distance from the temporal separation of a simulated pulse and echo. This innate cortical implementation of a purely computational processing mechanism for sonar ranging should enhance survival of juvenile bats when they first engage in active echolocation behaviour and flight.
A lamin in lower eukaryotes?
(2012)
Lamins are the major components of the nuclear lamina and serve not only as a mechanical support, but are also involved in chromatin organization, epigenetic regulation, transcription and mitotic events. Despite these universal tasks, lamins have so far been found only in metazoans. Yet, recently we have identified Dictyostelium NE81 as the first lamin-like protein in a lower eukaryote. Based on the current knowledge, we draw a model for nuclear envelope organization in Dictyostelium in this Extra View and we review the experimental data that justified this classification. Furthermore we provide unpublished data underscoring the requirement of posttranslational CaaX-box processing for proper protein localization at the nuclear envelope. Sequence comparison of NE81 sequences from four Dictyostelia with bona fide lamins illustrates the evolutional relationship between these proteins. Under certain conditions these usually unicellular social amoebae congregate to form a multicellular body. We propose that the evolution of the lamin-like NE81 went along with the invention of multicellularity.
The dynamic range of fiber-optic fluorescent probes such as single fibers and fiber bundles is calculated for strongly absorbing samples, such as process liquids, foodstuffs, and lubricants. The model assumes an excitation beam profile based on a Lambertian light source and uses analytical forms of the collection efficiency, followed by an Abel transformation and numerical integration. It is found that the effect of primary absorption of the excitation light and secondary absorption of the fluorescence is profound. For fiber bundles and bifurcated fiber probes, the upper accessible concentration limit is roughly given by the absorption length of the primary and secondary absorption. Fluorescence detectors that are placed at right angles to the excitation beam axis or collinear to the beam axis are equally strongly affected by secondary absorption. A probe in which the same fiber is used for excitation and for collection of the fluorescence emerges as the fiber probe with the largest accessible concentration range.
Photon Density Wave (PDW) spectroscopy was applied for temperature dependent monitoring of melting and crystallization of milk fat within homogenized fresh milk. As an in-line process analytical technique, PDW spectroscopy quantifies continuously the optical properties of turbid material, providing an insight into its structural processes. Here, the measured absorption coefficients reflect temperature as well as fat content of milk and the reduced scattering coefficients probe physical changes of the light scattering fat droplets and casein micelles. Thermal processing reveals breakpoints within the temperature trend of the reduced scattering coefficient of fat containing milk. Found at 16 degrees C and 24 degrees C while cooling and heating, respectively, they are associated to the phase transitions of milk fat. Continuous isothermal measurement of the optical coefficients showed that the crystallization process requires several hours. The strongly changing reduced scattering coefficient implies that the thermal history of milk will have a major impact on any method based on light scattering as quantitative analytical technique.
Dictyostelium centrosomes consist of a layered core structure surrounded by a microtubule-nucleating corona. At the G2/M transition, the corona dissociates and the core structure duplicates, yielding two spindle pole bodies. Finally, in telophase, the spindle poles mature into two new, complete centrosomes. CP55 was identified in a centrosomal proteome analysis. It is a component of the centrosomal core structure, and persists at the centrosome throughout the entire cell cycle. FRAP experiments revealed that during interphase the majority of centrosomal GFP-CP55 is immobile, which indicates a structural task of CP55 at the centrosome. The CP55null mutant is characterized by increased ploidy, a less structured, slightly enlarged corona, and by supernumerary, cytosolic MTOCs, containing only corona proteins and lacking a core structure. Live cell imaging showed that supernumerary MTOCs arise in telophase. Lack of CP55 also caused premature recruitment of the corona organizer CP148 to mitotic spindle poles, already in metaphase instead of telophase. Forces transmitted through astral microtubules may expel prematurely acquired or loosely attached corona fragments into the cytosol, where they act as independent MTOCs. CP55null cells were also impaired in growth, most probably due to difficulties in centrosome splitting during prophase. Furthermore, although they were still capable of phagocytosis, they appeared unable to utilize phagocytosed nutrients. This inability may be attributed to their partially disorganized Golgi apparatus.
The centrosome consists of a layered core structure surrounded by a microtubule-nucleating corona. A tight linkage through the nuclear envelope connects the cytosolic centrosome with the clustered centromeres within the nuclear matrix. At G2/M the corona dissociates, and the core structure duplicates, yielding two spindle poles. CP148 is a novel coiled coil protein of the centrosomal corona. GFP-CP148 exhibited cell cycle-dependent presence and absence at the centrosome, which correlates with dissociation of the corona in prophase and its reformation in late telophase. During telophase, GFP-CP148 formed cytosolic foci, which coalesced and joined the centrosome. This explains the hypertrophic appearance of the corona upon strong overexpression of GFP-CP148. Depletion of CP148 by RNAi caused virtual loss of the corona and disorganization of interphase microtubules. Surprisingly, formation of the mitotic spindle and astral microtubules was unaffected. Thus, microtubule nucleation complexes associate with centrosomal core components through different means during interphase and mitosis. Furthermore, CP148 RNAi caused dispersal of centromeres and altered Sun1 distribution at the nuclear envelope, suggesting a role of CP148 in the linkage between centrosomes and centromeres. Taken together, CP148 is an essential factor for the formation of the centrosomal corona, which in turn is required for centrosome/centromere linkage.
Characterization of NE81, the first lamin-like nucleoskeleton protein in a unicellular organism
(2012)
Krüger, Anne ; Batsios, Petros ; Baumann, Otto ; Luckert, Eva ; Schwarz, Heinz ; Stick, Reimer ; Meyer, Irene ; Gräf, Ralph
Lamins build the nuclear lamina and are required for chromatin organization, gene expression, cell cycle progression, and mechanical stabilization. Despite these universal functions, lamins have so far been found only in metazoans. We have identified protein NE81 in Dictyostelium, which has properties that justify its denomination as a lamin-like protein in a lower eukaryote. This is based on its primary structure, subcellular localization, and regulation during mitosis, and its requirement of the C-terminal CaaX box as a posttranslational processing signal for proper localization. Our knockout and overexpression mutants revealed an important role for NE81 in nuclear integrity, chromatin organization, and mechanical stability of cells. All our results are in agreement with a role for NE81 in formation of a nuclear lamina. This function is corroborated by localization of Dictyostelium NE81 at the nuclear envelope in human cells. The discovery of a lamin-like protein in a unicellular organism is not only intriguing in light of evolution, it may also provide a simple experimental platform for studies of the molecular basis of laminopathies.
Albrecht, Steve ; Janietz, Silvia ; Schindler, Wolfram ; Frisch, Johannes ; Kurpiers, Jona ; Kniepert, Juliane ; Inal, Sahika ; Pingel, Patrick ; Fostiropoulos, Konstantinos ; Koch, Norbert ; Neher, Dieter
A novel fluorinated copolymer (F-PCPDTBT) is introduced and shown to exhibit significantly higher power conversion efficiency in bulk heterojunction solar cells with PC70BM compared to the well-known low-band-gap polymer PCPDTBT. Fluorination lowers the polymer HOMO level, resulting in high open-circuit voltages well exceeding 0.7 V. Optical spectroscopy and morphological studies with energy-resolved transmission electron microscopy reveal that the fluorinated polymer aggregates more strongly in pristine and blended layers, with a smaller amount of additives needed to achieve optimum device performance. Time-delayed collection field and charge extraction by linearly increasing voltage are used to gain insight into the effect of fluorination on the field dependence of free charge-carrier generation and recombination. F-PCPDTBT is shown to exhibit a significantly weaker field dependence of free charge-carrier generation combined with an overall larger amount of free charges, meaning that geminate recombination is greatly reduced. Additionally, a 3-fold reduction in non-geminate recombination is measured compared to optimized PCPDTBT blends. As a consequence of reduced non-geminate recombination, the performance of optimized blends of fluorinated PCPDTBT with PC70BM is largely determined by the field dependence of free-carrier generation, and this field dependence is considerably weaker compared to that of blends comprising the non-fluorinated polymer. For these optimized blends, a short-circuit current of 14 mA/cm(2), an open-circuit voltage of 0.74 V, and a fill factor of 58% are achieved, giving a highest energy conversion efficiency of 6.16%. The superior device performance and the low band-gap render this new polymer highly promising for the construction of efficient polymer-based tandem solar cells.
Sphingosine-1-phosphate lyase (SPL) is the only known enzyme that irreversibly cleaves sphingosine-1-phosphate (S1P) into phosphoethanolamine and (2E)-hexadecenal during the final step of sphingolipid catabolism. Because S1P is involved in a wide range of physiological and diseased processes, determining the activity of the degrading enzyme is of great interest. Therefore, we developed two procedures based on liquid chromatography (LC) for analysing (2E)-hexadecenal, which is one of the two S1P degradation products. After separation, two different quantification methods were performed, tandem mass spectrometry (MS) and fluorescence detection. However, (2E)-hexadecenal as a long-chain aldehyde is not ionisable by electrospray ionisation (ESI) for MS quantification and has an insufficient number of corresponding double bonds for fluorescence detection. Therefore, we investigated 2-diphenylacetyl-1,3-indandione-1-hydrazone (DAIH) as a derivatisation reagent. DAIH transforms the aldehyde into an ionisable and fluorescent analogue for quantitative analysis. Our conditions were optimised to obtain the outstanding limit of detection (LOD) of 1 fmol per sample (30 mu L) for LC-MS/MS and 0.75 pmol per sample (200 mu l) for LC determination with fluorescence detection. We developed an extraction procedure to separate and concentrate (2E)-hexadecenal from biological samples for these measurements. To confirm our new methods, we analysed the (2E)-hexadecenal level of different cell lines and human plasma for the first time ever. Furthermore, we treated HT-29 cells with different concentrations of 4-deoxypyridoxine (DOP), which competitively inhibits pyridoxal-5-phosphate (P5P), an essential cofactor for SPL activity, and observed a significant decrease in (2E)-hexadecenal relative to the untreated cells.
During reading information is acquired from word(s) beyond the word that is currently looked at. It is still an open question whether such parafoveal information can influence the current viewing of a word, and if so, whether such parafoveal-on-foveal effects are attributable to distributed processing or to mislocated fixations which occur when the eyes are directed at a parafoveal word but land on another word instead. In two display-change experiments, we orthogonally manipulated the preview and target difficulty of word n+2 to investigate the role of mislocated fixations on the previous word n+1. When the eyes left word n, an easy or difficult word n+2 preview was replaced by an easy or difficult n+2 target word. In Experiment 1, n+2 processing difficulty was manipulated by means of word frequency (i.e., easy high-frequency vs. difficult low-frequency word n+2). In Experiment 2, we varied the visual familiarity of word n+2 (i.e., easy lower-case vs. difficult alternating-case writing). Fixations on the short word n+1, which were likely to be mislocated, were nevertheless not influenced by the difficulty of the adjacent word n+2, the hypothesized target of the mislocated fixation. Instead word n+1 was influenced by the preview difficulty of word n+2, representing a delayed parafoveal-on-foveal effect. The results challenge the mislocated-fixation hypothesis as an explanation of parafoveal-on-foveal effects and provide new insight into the complex spatial and temporal effect structure of processing inside the perceptual span during reading.
Preview fixation duration modulates identical and semantic preview benefit in Chinese reading
(2012)
Semantic preview benefit from parafoveal words is critical for proposals of distributed lexical processing during reading. Semantic preview benefit has been demonstrated for Chinese reading with the boundary paradigm in which unrelated or semantically related previews of a target word N + 1 are replaced by the target word once the eyes cross an invisible boundary located after word N (Yan et al., 2009); for the target word in position N + 2, only identical compared to unrelated-word preview led to shorter fixation times on the target word (Yan et al., in press). A reanalysis of these data reveals that identical and semantic preview benefits depend on preview duration (i.e., the fixation duration on the preboundary word). Identical preview benefit from word N + 1 increased with preview duration. The identical preview benefit was also significant for N + 2, but did not significantly interact with preview duration. The previously reported semantic preview benefit from word N + 1 was mainly due to single- or first-fixation durations following short previews. We discuss implications for notions of serial attention shifts and parallel distributed processing of words during reading.
Frasca, Stefano ; Rojas, Oscar ; Salewski, Johannes ; Neumann, Bettina ; Stiba, Konstanze ; Weidinger, Inez M. ; Tiersch, Brigitte ; Leimkühler, Silke ; Koetz, Joachim ; Wollenberger, Ursula
The present study reports a facile approach for sulfite biosensing, based on enhanced direct electron transfer of a human sulfite oxidase (hSO) immobilized on a gold nanoparticles modified electrode. The spherical core shell AuNPs were prepared via a new method by reduction of HAuCl4 with branched poly(ethyleneimine) in an ionic liquids resulting particles with a diameter less than 10 nm. These nanoparticles were covalently attached to a mercaptoundecanoic acid modified Au-electrode where then hSO was adsorbed and an enhanced interfacial electron transfer and electrocatalysis was achieved. UV/Vis and resonance Raman spectroscopy, in combination with direct protein voltammetry, are employed for the characterization of the system and reveal no perturbation of the structural integrity of the redox protein. The proposed biosensor exhibited a quick steady-state current response, within 2 s, a linear detection range between 0.5 and 5.4 mu M with a high sensitivity (1.85 nA mu M-1). The investigated system provides remarkable advantages in the possibility to work at low applied potential and at very high ionic strength. Therefore these properties could make the proposed system useful in the development of bioelectronic devices and its application in real samples.
Wöhl-Bruhn, Stefanie ; Badar, Muhammad ; Bertz, Andreas ; Tiersch, Brigitte ; Koetz, Joachim ; Menzel, Henning ; Müller, Peter P. ; Bunjes, Heike
Hydrogel systems based on hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA) or hydroxyethyl starch methacrylate (HES-MA) were used to assess the protein release behavior. Here, we analyzed the in vitro release of FITC-anti-human antibodies incorporated in either HES-P(EG)(6)MA or HES-MA hydrogel delivery systems in PBS or human serum. In addition, hydrogel disks and microparticles prepared from the two polymers were subcutaneously implanted in BALB/c mice. The in vivo release of FITC-IgG was non-invasively monitored by an in vivo imaging system (IVIS 200) over a time period of up to 3 months. The imaging system allowed to asses individual animals over time, therefore only a small number of animals was required to obtain high quality data. The reduction in fluorescence intensity at the site of administration was compared to in vitro release profiles. These investigations demonstrated a sustained release from HES-MA hydrogel disks compared to rapidly degrading HES-P(EG)(6)MA disks and microparticles. The sustained release from HES-MA disks could be further optimized by using increased polymer concentrations. Human serum as in vitro release medium reflected better the in vivo release from HES-P(EG)(6)MA systems than PBS, suggesting that the presence of organic substances like proteins or lipids may play a significant role for the release kinetics.
Koeth, Anja ; Tiersch, Brigitte ; Appelhans, Dietmar ; Gradzielski, Michael ; Cölfen, Helmut ; Koetz, Joachim
The synthesis of ultrafine gold nanoparticles in presence of maltose-modified hyperbranched poly(ethyleneimines) (PEI) is described. The polymer acted as both a reducing and stabilising agent in the particle formation process. The nanoparticles were characterized by means of dynamic light scattering (DLS), transmission electron microscopy (TEM), analytical ultracentrifugation (AUC), small-angle x-ray scattering (SAXS), and small-angle neutron scattering (SANS). The mechanism of nanoparticle formation can be described in two steps. The reduction process of the Au3+ ions located in the inner coil region of the hyperbranched PEI led to the formation of a compact gold core, and is accompanied by a collapse of the polymer coil. Therefore, in the subsequent reduction process a gold-polymer hybrid shell is formed. By using the PEI of higher molar mass, core-shell gold nanoparticles of about 3.6 nm size with a more narrow size distribution and special fluorescence behavior could be synthesized.
Schattauer, Sylvia ; Reinhold, Beate ; Albrecht, Steve ; Fahrenson, Christoph ; Schubert, Marcel ; Janietz, Silvia ; Neher, Dieter
In this work, a nonaqueous method is used to fabricate thin TiO2 layers. In contrast to the common aqueous sol-gel approach, our method yields layers of anatase nanocrystallites already at low temperature. Raman spectroscopy, electron microscopy and charge extraction by linearly increasing voltage are employed to study the effect of sintering temperature on the structural and electronic properties of the nanocrystalline TiO2 layer. Raising the sintering temperature from 120 to 600 A degrees C is found to alter the chemical composition, the layer's porosity and its surface but not the crystal phase. The room temperature mobility increases from 2 x 10(-6) to 3 x 10(-5) cm(2)/Vs when the sinter temperature is increased from 400 to 600 A degrees C, which is explained by a better interparticle connectivity. Solar cells comprising such nanoporous TiO2 layers and a soluble derivative of cyclohexylamino-poly(p-phenylene vinylene) were fabricated and studied with regard to their structural and photovoltaic properties. We found only weak polymer infiltration into the oxide layer for sintering temperatures up to 550 A degrees C, while the polymer penetrated deeply into titania layers that were sintered at 600 A degrees C. Best photovoltaic performance was reached with a nanoporous TiO2 film sintered at 550 A degrees C, which yielded a power conversion efficiency of 0.5 %. Noticeably, samples with the TiO2 layer dried at 120 A degrees C displayed short-circuit currents and open circuit voltages only about 15-20 % lower than for the most efficient devices, meaning that our nonaqueous route yields titania layers with reasonable transport properties even at low sintering temperatures.
Henkel, Janin ; Frede, Katja ; Schanze, Nancy ; Vogel, Heike ; Schürmann, Annette ; Spruß, Astrid ; Bergheim, Ina ; Püschel, Gerhard Paul
Hepatic steatosis is recognized as hepatic presentation of the metabolic syndrome. Hyperinsulinaemia, which shifts fatty acid oxidation to de novo lipogenesis and lipid storage in the liver, appears to be a principal elicitor particularly in the early stages of disease development. The impact of PGE(2), which has previously been shown to attenuate insulin signaling and hence might reduce insulin-dependent lipid accumulation, on insulin-induced steatosis of hepatocytes was studied. The PGE(2)-generating capacity was enhanced in various obese mouse models by the induction of cyclooxygenase 2 and microsomal prostaglandin E-synthases (mPGES1, mPGES2). PGE(2) attenuated the insulin-dependent induction of SREBP-1c and its target genes glucokinase and fatty acid synthase. Nevertheless, PGE(2) enhanced incorporation of glucose into hepatic triglycerides synergistically with insulin. This was most likely due to a combination of a PGE(2)-dependent repression of (1) the key lipolytic enzyme adipose triglyceride lipase, (2) carnitine-palmitoyltransferase 1, a key regulator of mitochondrial beta-oxidation, and (3) microsomal transfer protein, as well as (4) apolipoprotein B, key components of the VLDL synthesis. Repression of PGC1 alpha, a common upstream regulator of these genes, was identified as a possible cause. In support of this hypothesis, overexpression of PGC1 alpha completely blunted the PGE(2)-dependent fat accumulation. PGE(2) enhanced lipid accumulation synergistically with insulin, despite attenuating insulin signaling and might thus contribute to the development of hepatic steatosis. Induction of enzymes involved in PGE(2) synthesis in in vivo models of obesity imply a potential role of prostanoids in the development of NAFLD and NASH. Laboratory Investigation (2012) 92, 1597-1606; doi:10.1038/labinvest.2012.128; published online 10 September 2012
Hesse, Deike ; Jaschke, Alexander ; Kanzleiter, Timo ; Witte, Nicole ; Augustin, Robert ; Hommel, Angela ; Püschel, Gerhard Paul ; Petzke, Klaus-Jürgen ; Joost, Hans-Georg ; Schupp, Michael ; Schürmann, Annette
The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) is located at the trans-Golgi compartment and regulates the recruitment of Arf-like 1 (ARL1) and its effector golgin-245 to this compartment. Here, we show that liver-specific knockout of Arfrp1 in the mouse (Arfrp1(liv-/-)) resulted in early growth retardation, which was associated with reduced hepatic insulin-like growth factor 1 (IGF1) secretion. Accordingly, suppression of Arfrp1 in primary hepatocytes resulted in a significant reduction of IGF1 release. However, the hepatic secretion of IGF-binding protein 2 (IGFBP2) was not affected in the absence of ARFRP1. In addition, Arfrp1(liv-/-) mice exhibited decreased glucose transport into the liver, leading to a 50% reduction of glycogen stores as well as a marked retardation of glycogen storage after fasting and refeeding. These abnormalities in glucose metabolism were attributable to reduced protein levels and intracellular retention of the glucose transporter GLUT2 in Arfrp1(liv-/-) livers. As a consequence of impaired glucose uptake into the liver, the expression levels of carbohydrate response element binding protein (ChREBP), a transcription factor regulated by glucose concentration, and its target genes (glucokinase and pyruvate kinase) were markedly reduced. Our data indicate that ARFRP1 in the liver is involved in the regulation of IGF1 secretion and GLUT2 sorting and is thereby essential for normal growth and glycogen storage.
Spruss, Astrid ; Henkel, Janin ; Kanuri, Giridhar ; Blank, Daniela ; Püschel, Gerhard Paul ; Bischoff, Stephan C. ; Bergheim, Ina
As significant differences between sexes were found in the susceptibility to alcoholic liver disease in human and animal models, it was the aim of the present study to investigate whether female mice also are more susceptible to the development of nonalcoholic fatty liver disease (NAFLD). Male and female C57BL/6J mice were fed either water or 30% fructose solution ad libitum for 16 wks. Liver damage was evaluated by histological scoring. Portal endotoxin levels and markers of Kupffer cell activation and insulin resistance, plasminogen activator inhibitor 1 (PAI-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) were measured in the liver. Adiponectin mRNA expression was determined in adipose tissue. Hepatic steatosis was almost similar between male and female mice; however, inflammation was markedly more pronounced in livers of female mice. Portal endotoxin levels, hepatic levels of myeloid differentiation primary response gene (88) (MyD88) protein and of 4-hydroxynonenal protein adducts were elevated in animals with NAFLD regardless of sex. Expression of insulin receptor substrate 1 and 2 was decreased to a similar extent in livers of male and female mice with NAFLD. The less pronounced susceptibility to liver damage in male mice was associated with a superinduction of hepatic pAMPK in these mice whereas, in livers of female mice with NAFLD, PAI-1 was markedly induced. Expression of adiponectin in visceral fat was significantly lower in female mice with NAFLD but unchanged in male mice compared with respective controls. In conclusion, our data suggest that the sex-specific differences in the susceptibility to NAFLD are associated with differences in the regulation of the adiponectin-AMPK-PAI-1 signaling cascade. Online address: http://www.molmed.Org doi: 10.2119/molmed.2012.00223