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Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.
Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s
(2015)
Crystal structures of indeno[1,2-d]imidazoles. XIth European Crystallographic Meeting, Vienna 1988
(1988)
Fast and Automated Testing of Different Air Filter Media / Mölter, W. ; Helsper, C. ; Kaminski, S.
(1989)
Fast and Automated Testing of Different Air Filter Media / Mölter, W. ; Helsper, C. ; Kaminski, S.
(1989)
Fast, Automated Testing of Different Air Filter Media / Mölter, W. ; Helsper, C. ; Kaminski, S.
(1992)
Erzeugung von Prüfaerosolen für die Kalibrierung von optischen Partikelmeßverfahren nach VDI 3491
(1989)
Calibration of the Polytec HC-15 and HC-70 Optical Particle Counters / Fißan, H. J. ; Helsper, C.
(1983)
Evaluation of Particle Size Distributions by Means of Particle Counters / Fißan, H. J. ; Helsper, C.
(1979)
Partikelmesstechnik
(2002)
Differential modulation of valence and arousal in high-alexithymic and low-alexithymic individuals
(2010)
High-alexithymic individuals are characterized by an impaired ability to identify and communicate emotions whereas low-alexithymic individuals have a wide-ranging ability to deal with emotions. This study examined the hypothesis that valence and arousal modifications of emotional stimuli differentially modulate cortical regions in high-alexithymic and low-alexithymic individuals. To this end, 28 high-alexithymic and 25 low-alexithymic individuals were investigated with event-related fMRI using visual emotional stimuli. We found differential neural activations in the dorsal anterior cingulate, the insula and the amygdala. We suggest that these differences may account for the impaired ability of high-alexithymic individuals to appropriately handle emotional stimuli.
Background: One of the most prominent neurobiological models of alexithymia assumes an altered function of the anterior cingulate cortex (ACC) as the crucial neural correlate of alexithymia. So far functional imaging studies have yielded inconclusive results. Therefore, we tested this hypothesis in healthy alexithymics and nonalexithymics in an event-related fMRI study.
Methods: Thirty high- and 30 low-alexithymic right-handed male subjects (selected by the 20-item Toronto Alexithymia Scale, TAS-20) were investigated with event-related fMRI using a picture viewing paradigm. The stimuli consisted of happy, fearful and neutral facial expressions (Ekman-Friesen) as well as positive, negative and neutral pictures from the International Affective Picture System.
Results: Contrasting the high-alexithymic with the low-alexithymic group we observed increased activation of the supragenual ACC for different emotional valences as well as for different emotional stimuli. Moreover, there was a positive correlation of the ACC with the individual TAS-20 scores but no correlations with the individual Beck Depression Inventory scores. Additionally, there was no difference in activity of the amygdala.
Conclusions: We demonstrated that the supragenual ACC is constantly activated more strongly in alexithymic subjects and that this activation is related to the symptoms of alexithymia and not to associated symptoms such as depression. Therefore, our findings support the hypothesis of an altered function of the ACC in alexithymia.
Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt %, while sheets with a thickness of 0.2–0.5 mm appear flexible already at 7.5 wt %. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials.
Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃–(CH₂CH (OCO(CH₂)ₘCH₃))ₙ–Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated.
All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain.
Within the Crystal Clear Collaboration four centres are developing 2nd generation high performance small animal PET scanners for different kinds of animals and medical applications. The first prototypes are PMT-based systems including depth of interaction (DOI) detection by using a phoswich layer of LSO and LuYAP. The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in FOVs caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN) was used. The simulations have shown that all PMT designs with one-to-one coupling of crystals have a very nonlinear axial sensitivity profile. By shifting every other PMT 1/4 of a PMT length in axial direction the sampling of the FOVs became more homogeneous. At an energy threshold of 350keV the regression coefficient increases from 0.818 for the non-shifted to 0.993 for the shifted design. Simulations of a point source centred in the FOV (threshold: 350keV) resulted in sensitivities of 4.2% for a 4×20PMT (LSO/LuYAP a 10mm) and 3.8% for a 4×16PMT (LSO/LuYAP a 8mm) ring design. The 3D-MLEM reconstruction of a point source shows the enormous improvement of resolution using a crystal double layer with DOI (3.1mm at 40mm from CFOV) instead of a 20mm single layer (11.9mm).
Within the Crystal Clear Collaboration (CCC), four centers are developing second generation high performance small animal positron emission tomography (PET) scanners for different kinds of animals and medical applications. The first prototypes are photomultiplier tube (PMT)-based systems including depth of interaction (DOI) detection by using a phoswich layer of lutetium oxyorthosilicate (LSO) and lutetium yttrium aluminum perovskite (LuYAP). The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in fields of view (FOVs) caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN, Geneva, Switzerland) was used.
Rechnerunterstuetzte Aufbereitung von Finite-Elemente-Rechenmodellen-Erfassung der Bauteilgeometrie
(1977)
Rechnerunterstuetzte Aufbereitung von Finite-Elemente-Rechenmodellen -Erstellen der FEM-Netzwerke
(1977)
STEP bietet mehr
(1992)
The optimization of light output and energy resolution of scintillators is of special interest for the development of high resolution and high sensitivity PET. The aim of this work is to obtain statistically reliable results concerning optimal surface treatment of scintillation crystals and the selection of reflector material. For this purpose, raw, mechanically polished and etched LSO crystals (size 2×2×10 mm3) were combined with various reflector materials (Teflon tape, Teflon matrix, BaSO4) and exposed to a 22Na source. In order to ensure the statistical reliability of the results, groups of 10 LSO crystals each were measured for all combinations of surface treatment and reflector material. Using no reflector material the light output increased up to 551±35% by mechanical polishing the surface compared to 100±5% for raw crystals. Etching the surface increased the light output to 441±29%. The untreated crystals had an energy resolution of 24.6±4.0%. By mechanical polishing the surface it was possible to achieve an energy resolution of 13.2±0.8%, by etching of 14.8±0.7%. In combination with BaSO4 as reflector material the maximum increase of light output has been established to 932±57% for mechanically polished and 895±61% for etched crystals. The combination with BaSO4 also caused the best improvement of the energy resolution up to 11.6±0.2% for mechanically polished and 12.2±0.3% for etched crystals. Relating to the light output there was no significant statistical difference between the two surface treatments in combination with BaSO4. In contrast to this, the statistical results of the energy resolution have shown the combination of mechanical polishing and BaSO4 as the optimum.
BACKGROUND: Muscle stretch reflexes are widely considered to beneficially influence joint stability and power generation in the lower limbs. While in the upper limbs and especially in the muscles surrounding the shoulder joint such evidence is lacking. OBJECTIVE: To quantify the electromyographical response in the muscles crossing the shoulder of specifically trained overhead athletes to an anterior perturbation force. METHODS: Twenty healthy male participants performed six sets of different external shoulder rotation stretches on an isokinetic dynamometer over a range of amplitudes and muscle pre-activation moment levels. All stretches were applied with a dynamometer acceleration of 10,000∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexes were not observed in all experimental conditions. The reflex latencies revealed a significant muscle main effect (F (2,228) = 99.31, p< 0.001; η2= 0.466; f= 0.934) and a pre-activation main effect (F (1,228) = 142.21, p< 0.001; η2= 0.384; f= 1.418). The stretch reflex amplitude yielded a significant pre-activation main effect (F (1,222) = 470.373, p< 0.001; η2= 0.679; f= 1.454). CONCLUSION: Short latency muscle reflexes showed a tendency to an anterior to posterior muscle recruitment whereby the main internal rotator muscles of the shoulder revealed the most consistent results.
BACKGROUND: Muscle stretch reflexes are widely used to examine neural muscle function. The knowledge of reflex response in muscles crossing the shoulder is limited. OBJECTIVE: To quantify reflex modulation according to various subject postures and different procedures of muscle pre-activation steering. METHODS: Thirteen healthy male participants performed two sets of external shoulder rotation stretches in various positions and with different procedures of muscle pre-activation steering on an isokinetic dynamometer over a range of two different pre-activation levels. All stretches were applied with a dynamometer acceleration of 104∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexive response was observed in all tested muscles in all experimental conditions. The reflex elicitation rate revealed a significant muscle main effect (F (5,288) = 2.358, ρ= 0.040; η2= 0.039; f= 0.637) and a significant test condition main effect (F (1,288) = 5.884, ρ= 0.016; η2= 0.020; f= 0.143). Reflex latency revealed a significant muscle pre-activation level main effect (F (1,274) = 5.008, ρ= 0.026; η2= 0.018; f= 0.469). CONCLUSION: Muscular reflexive response was more consistent in the primary internal rotators of the shoulder. Supine posture in combination with visual feedback of muscle pre-activation level enhanced the reflex elicitation rate.
Test-retest reliability of the internal shoulder rotator muscles' stretch reflex in healthy men
(2021)
Until now the reproducibility of the short latency stretch reflex of the internal rotator muscles of the glenohumeral joint has not been identified. Twenty-three healthy male participants performed three sets of external shoulder rotation stretches with various pre-activation levels on two different dates of measurement to assess test-retest reliability. All stretches were applied with a dynamometer acceleration of 104°/s2 and a velocity of 150°/s. Electromyographical response was measured via surface EMG. Reflex latencies showed a pre-activation effect (ƞ2 = 0,355). ICC ranged from 0,735 to 0,909 indicating an overall “good” relative reliability. SRD 95% lay between ±7,0 to ±12,3 ms.. The reflex gain showed overall poor test-retest reproducibility. The chosen methodological approach presented a suitable test protocol for shoulder muscles stretch reflex latency evaluation. A proof-of-concept study to validate the presented methodical approach in shoulder involvement including subjects with clinically relevant conditions is recommended.
Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 Å as well as in complex with CoA at a resolution of 1.59 Å. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called “hot dog fold” which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all “hot dog fold” proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041–2053. © 2014 Wiley Periodicals, Inc.
The recently discovered first hyperbolic objects passing through the Solar System, 1I/’Oumuamua and 2I/Borisov, have raised the question about near term missions to Interstellar Objects. In situ spacecraft exploration of these objects will allow the direct determination of both their structure and their chemical and isotopic composition, enabling an entirely new way of studying small bodies from outside our solar system. In this paper, we map various Interstellar Object classes to mission types, demonstrating that missions to a range of Interstellar Object classes are feasible, using existing or near-term technology. We describe flyby, rendezvous and sample return missions to interstellar objects, showing various ways to explore these bodies characterizing their surface, dynamics, structure and composition. Their direct exploration will constrain their formation and history, situating them within the dynamical and chemical evolution of the Galaxy. These mission types also provide the opportunity to explore solar system bodies and perform measurements in the far outer solar system.
The recently discovered first high velocity hyperbolic objects passing through the Solar System, 1I/'Oumuamua and 2I/Borisov, have raised the question about near term missions to Interstellar Objects. In situ spacecraft exploration of these objects will allow the direct determination of both their structure and their chemical and isotopic composition, enabling an entirely new way of studying small bodies from outside our solar system. In this paper, we map various Interstellar Object classes to mission types, demonstrating that missions to a range of Interstellar Object classes are feasible, using existing or near-term technology. We describe flyby, rendezvous and sample return missions to interstellar objects, showing various ways to explore these bodies characterizing their surface, dynamics, structure and composition. Interstellar objects likely formed very far from the solar system in both time and space; their direct exploration will constrain their formation and history, situating them within the dynamical and chemical evolution of the Galaxy. These mission types also provide the opportunity to explore solar system bodies and perform measurements in the far outer solar system.
This paper examines the positive and negative aspects of a range of interpretations of nearest-neighbours models. Measures-oriented and distributionoriented verification methods are applied to categorial, probabilistic and descriptive interpretations of nearest neighbours used operationally in avalanche forecasting in Scotland and Switzerland. The dependence of skill and accuracy measures on base rate is illustrated. The purpose of the forecast and the definition of events are important variables in determining the quality of the forecast. A discussion of the application of different interpretations in operational avalanche forecasting is presented.
It has been shown that muscle fascicle curvature increases with increasing contraction level and decreasing muscle–tendon complex length. The analyses were done with limited examination windows concerning contraction level, muscle–tendon complex length, and/or intramuscular position of ultrasound imaging. With this study we aimed to investigate the correlation between fascicle arching and contraction, muscle–tendon complex length and their associated architectural parameters in gastrocnemius muscles to develop hypotheses concerning the fundamental mechanism of fascicle curving. Twelve participants were tested in five different positions (90°/105°*, 90°/90°*, 135°/90°*, 170°/90°*, and 170°/75°*; *knee/ankle angle). They performed isometric contractions at four different contraction levels (5%, 25%, 50%, and 75% of maximum voluntary contraction) in each position. Panoramic ultrasound images of gastrocnemius muscles were collected at rest and during constant contraction. Aponeuroses and fascicles were tracked in all ultrasound images and the parameters fascicle curvature, muscle–tendon complex strain, contraction level, pennation angle, fascicle length, fascicle strain, intramuscular position, sex and age group were analyzed by linear mixed effect models. Mean fascicle curvature of the medial gastrocnemius increased with contraction level (+5 m−1 from 0% to 100%; p = 0.006). Muscle–tendon complex length had no significant impact on mean fascicle curvature. Mean pennation angle (2.2 m−1 per 10°; p < 0.001), inverse mean fascicle length (20 m−1 per cm−1; p = 0.003), and mean fascicle strain (−0.07 m−1 per +10%; p = 0.004) correlated with mean fascicle curvature. Evidence has also been found for intermuscular, intramuscular, and sex-specific intramuscular differences of fascicle curving. Pennation angle and the inverse fascicle length show the highest predictive capacities for fascicle curving. Due to the strong correlations between pennation angle and fascicle curvature and the intramuscular pattern of curving we suggest for future studies to examine correlations between fascicle curvature and intramuscular fluid pressure.