Modulation of T cell Activation with Nano- and Micronanopatterned Antigen Arrays

The human immune system is a multi-talented composition of a variety of interacting elements trying to protect the host from any kind of disease. Much research has been done to elucidate a key event of this complex defense strategy, which is the activation of T cells resulting from the formation of a temporary synapse between a T cell and an antigen presenting cell. During this intercellular contact the T cell obtains pathogen-related information in order to initiate specific steps for averting the disease. In the presented work, we introduce a novel, bio-functional substrate system simulating the antigen presenting cell’s surface. The engineered platform provides defined micro- and nano-scaled presentation of crucial proteins as well as control over substrate compliance. This system enables the possibility to investigate T cell activation and synapse formation under controlled conditions. It could be demonstrated that T cells show activation-related behavior when interacting with such substrates; they adhere, polarize and start to release signaling molecules. These events prove that the substrates can substitute for the antigen presenting cell and are able to modulate the activation process of T cells. It was shown that T cells are sensitive to a surface density of 90–140 stimulating molecules per μm2, but only if presented over the entire cell-surface contact area. An adhesive background consisting of proteins which support the adhesion process significantly decrease this threshold value. These insights contribute to a deeper understanding of the complex process of T cell activation and support the development of novel therapies employing the body’s own defense system to control diseases

The war crimes trial against German Industrialist Friedrich Flick et al - a legal analysis and critical evaluation

Magister Legum - LLMThis research paper is an analysis of the case United States v Flick et al which took place in 1947 in Nuremberg, Germany. Friedrich Flick, a powerful German industrialist, and several high ranking officials of his firm were tried by a United States military tribunal for war crimes and crimes against humanity committed during the Third Reich. The proceedings and the decision itself are the subject of a critical examination, including an investigation of the factual and legal background. The trial will be regarded in the historical context of prosecutions against German industrialists after World War II. Seen from present-day perspective, the question will be raised whether any conclusions can be drawn from the Flick case in respect of the substance of present-day international criminal law.South Afric

In situ static and dynamic light scattering and scanning electron microscopy study on the crystallization of the dense zinc imidazolate framework ZIF-zni

The kinetics and mechanism of crystallization of the dense zinc imidazolate framework with zni topology, from comparatively dilute methanol solutions containing Zn(NO3)·6H2O and imidazole with variation of the zinc-to-imidazole ratio, were followed in situ by time-resolved static and dynamic light scattering. The light scattering data revealed that metastable primary particles of about 100 nm in diameter form rapidly upon mixing the component solutions. After a lag time that is dependent on the imidazole concentration, the primary particles aggregate into secondary particles by a monomer addition mechanism with the primary particles as the monomers. Complementary scanning electron microscopy revealed that further evolution of the secondary particles is a complex process involving polycrystalline intermediates, the non-spherical morphologies of which depend on the initial zinc-to-imidazole ratio. Time and location of the first appearance of crystalline order could so far not be established. The pure-phase ZIF-zni crystals obtained after 240 min are twins. The aspect ratio of the tetragonal crystals can be controlled via the zinc-to-imidazole ratio. © 2011 The Owner Societies

The Complexity of Packing Edge-Disjoint Paths

We introduce and study the complexity of Path Packing. Given a graph G and a list of paths, the task is to embed the paths edge-disjoint in G. This generalizes the well known Hamiltonian-Path problem. Since Hamiltonian Path is efficiently solvable for graphs of small treewidth, we study how this result translates to the much more general Path Packing. On the positive side, we give an FPT-algorithm on trees for the number of paths as parameter. Further, we give an XP-algorithm with the combined parameters maximal degree, number of connected components and number of nodes of degree at least three. Surprisingly the latter is an almost tight result by runtime and parameterization. We show an ETH lower bound almost matching our runtime. Moreover, if two of the three values are constant and one is unbounded the problem becomes NP-hard. Further, we study restrictions to the given list of paths. On the positive side, we present an FPT-algorithm parameterized by the sum of the lengths of the paths. Packing paths of length two is polynomial time solvable, while packing paths of length three is NP-hard. Finally, even the spacial case Exact Path Packing where the paths have to cover every edge in G exactly once is already NP-hard for two paths on 4-regular graphs

Rapid recycling of glutamate transporters on the astroglial surface.

Glutamate uptake by astroglial transporters confines excitatory transmission to the synaptic cleft. The efficiency of this mechanism depends on the transporter dynamics in the astrocyte membrane, which remains poorly understood. Here, we visualise the main glial glutamate transporter GLT1 by generating its pH-sensitive fluorescent analogue, GLT1-SEP. Fluorescence recovery after photobleaching-based imaging shows that 70-75% of GLT1-SEP dwell on the surface of rat brain astroglia, recycling with a lifetime of ~22 s. Genetic deletion of the C-terminus accelerates GLT1-SEP membrane turnover while disrupting its surface pattern, as revealed by single-molecule localisation microscopy. Excitatory activity boosts surface mobility of GLT1-SEP, involving its C-terminus, metabotropic glutamate receptors, intracellular Ca2+, and calcineurin-phosphatase activity, but not the broad-range kinase activity. The results suggest that membrane turnover, rather than lateral diffusion, is the main 'redeployment' route for the immobile fraction (20-30%) of surface-expressed GLT1. This finding reveals an important mechanism helping to control extrasynaptic escape of glutamate

Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test

Purpose: To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). Methods: Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. Results: Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (<0.5mm). In the 1-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline. Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD 0.56), as did eyes with high (≥0.5mm) angle sizes (0.82 logMAR (SD 0.53). UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR (SD 0.13; p=0.019)). Conclusion: Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes. Keywords: Angle alpha; Angle kappa; Decision-making; Multifocal intraocular lens; Refractive lens surgery

Attentional processing of pain faces and other emotional faces in chronic pain–an eye-tracking study

Altered attentional processing of pain-associated stimuli–which might take the form of either avoidance or enhanced vigilance–is thought to be implicated in the development and maintenance of chronic pain. In contrast to reaction time tasks like the dot probe, eye tracking allows for tracking the time course of visual attention and thus differentiating early and late attentional processes. Our study aimed at investigating visual attention to emotional faces in patients with chronic musculoskeletal pain (N = 20) and matched pain-free controls (N = 20). Emotional faces (pain, angry, happy) were presented in pairs with a neutral face for 2000 ms each. Three parameters were determined: First fixation probabilities, fixation durations (overall and divided in four 500 ms intervals) and a fixation bias score as the relative fixation duration of emotional faces compared to neutral faces. There were no group differences in any of the parameters. First fixation probabilities were lower for pain faces than for angry faces. Overall, we found longer fixation duration on emotional compared to neutral faces (‘emotionality bias’), which is in accord with previous research. However, significant longer fixation duration compared to the neutral face was detected only for happy and angry but not for pain faces. In addition, fixation durations as well as bias scores yielded evidence for vigilant-avoidant processing of pain faces in both groups. These results suggest that attentional bias towards pain-associated stimuli might not generally differentiate between healthy individuals and chronic pain patients. Exaggerated attentional bias in patients might occur only under specific circumstances, e.g., towards stimulus material specifically relating to the specific pain of the patients under study or under high emotional distress

Human neutrophils communicate remotely via calcium-dependent glutamate-induced glutamate release

Summary Neutrophils are white blood cells that are critical to acute inflammatory and adaptive immune responses. Their swarming-pattern behavior is controlled by multiple cellular cascades involving calcium-dependent release of various signaling molecules. Previous studies have reported that neutrophils express glutamate receptors and can release glutamate but evidence of direct neutrophil-neutrophil communication has been elusive. Here, we hold semi-suspended cultured human neutrophils in patch-clamp whole-cell mode to find that calcium mobilization induced by stimulating one neutrophil can trigger an N-methyl-D-aspartate (NMDA) receptor-driven membrane current and calcium signal in neighboring neutrophils. We employ an enzymatic-based imaging assay to image, in real time, glutamate release from neutrophils induced by glutamate released from their neighbors. These observations provide direct evidence for a positive-feedback inter-neutrophil communication that could contribute to mechanisms regulating communal neutrophil behavior

Analysis of results on improved welded joints

Recents studies have shown that the use of improvement techniques on welds allows an increase in the level of admissible fatigue strength (even more than 100%). The aim of this study was to collect and validate literature data, create a data base containing the joint characteristics and fatigue results, make a statistical analysis of the data in order to quantify the effect of parameters influencing the fatigue strength and propose new S-N curves which are compared to those given in Eurocode 3. Four improvement techniques (grinding, TIG dressing, hammer peening, shot peening) and four joint types (butt, T joints, cruciform and longitudinal joints) were taken into account. Joint thicknesses less than 25 mm loaded in air with a stress ratio R between 0 and 0.1 were selected. Three classes of yield strength for the base metal were considered: 600. All S-N curves were above those of as-welded assemblies. The best results were obtained with hammer peening. The larger increase in the fatigue strength due to the use of improvement techniques was due to the occurrence of an initiation phase in addition to the crack propagation phase. During the initiation phase, the extension of existing crack-like defects is slowed down or even stopped. The duration of this phase increases with the total fatigue life