Biomedical subjects
Publications and source records attributed to Stephan Haas.
A microscopic, nonlocal response theory is developed to model the interaction of electromagnetic radiation with inhomogeneous nanoscale clusters. The breakdown of classical continuum-field Mie theory is demonstrated at a critical coarse-graining threshold, below which macroscopic plasmon resonances are replaced by molecular excitations with suppressed spectral intensity.
In disordered spin systems with antiferromagnetic Heisenberg exchange, transitions into and out of a magnetic-field-induced ordered phase pass through unique regimes. Using quantum Monte Carlo simulations to study the zero-temperature behavior, these intermediate regions are determined to be Bose-glass phases. The localization of field-induced triplons causes a finite compressibility and, hence, glassiness in the disordered phase.
The field-induced antiferromagnetic ordering in systems of weakly coupled S = 1/2 dimers at zero temperature can be described as a Bose-Einstein condensation of triplet quasiparticles (singlet quasiholes) in the ground state. For the case of a Heisenberg bilayer, it is here shown how the above picture is altered in the presence of site dilution of the magnetic lattice. Geometric randomness leads to quantum localization of the quasiparticles or quasiholes and to an extended Bose-glass phase in a realistic disordered model. This localization phenomenon drives the system towards a quantum-disordered phase well before the classical geometric percolation threshold is reached.
The interplay of geometric randomness and strong quantum fluctuations is an exciting topic in quantum many-body physics, leading to the emergence of novel quantum phases in strongly correlated electron systems. Recent investigations have focused on the case of homogeneous site and bond dilution in the quantum antiferromagnet on the square lattice, reporting a classical geometric percolation transition between magnetic order and disorder. In this study we show how inhomogeneous bond dilution leads to percolative quantum phase transitions, which we have studied extensively by quantum Monte Carlo simulations. Quantum percolation introduces a new class of two-dimensional spin liquids, characterized by an infinite percolating network with vanishing antiferromagnetic order parameter.
Making use of exact results and quantum Monte Carlo data for the entanglement of formation, we show that the ground state of anisotropic two-dimensional S=1/2 antiferromagnets in a uniform field takes the classical-like form of a product state for a particular value and orientation of the field, at which the purely quantum correlations due to entanglement disappear. Analytical expressions for the energy and the form of such states are given, and a novel type of exactly solvable two-dimensional quantum models is therefore singled out. Moreover, we show that the field-induced quantum phase transition present in the models is unambiguously characterized by a cusp minimum in the pairwise-to-global entanglement ratio R, marking the quantum-critical enhancement of multipartite entanglement.
Permanent alcohol abuse may lead to chronic liver injury with deleterious sequelae such as liver cirrhosis and hepatocellular carcinoma. Mechanisms of fibrogenesis encompass recruitment of inflammatory cells at the site of injury and cytokine mediated activation of hepatic stellate cells (HSC) with accumulation of interstitial collagens. HSC transdifferentiation and accompanying apoptosis result in destruction of liver architecture and are therefore key steps of disease progression. TGF-beta represents the main profibrogenic cytokine in liver fibrosis and other fibroproliferative disorders by inducing extracellular matrix deposition as part of the wound healing response. In parallel, TGF-beta triggers hepatocytes that are strongly responsive for this cytokine, to undergo apoptosis, thereby providing space for HSC proliferation and generation of a collagenous matrix. Anti TGF-beta approaches were established and successfully utilized for the treatment of experimental fibrogenesis. Dominant negative TGF-beta receptors (TbetaR), generated by fusing the Fc domain of human IgG and the N-terminal (extracellular) fragment of TbetaRII (Fc:TbetaRII) were applied to suppress fibrosis. Similarly TGF-beta binding proteins like decorin, antagonistic cytokines such as bone morphogenetic protein-7, hepatocyte growth factor, IL-10, or IFN-gamma were as efficient as camostat mesilate, a protease inhibitor that possibly abrogated proteolytic activation of TGF-beta. Further, our group recently overexpressed Smad7 in bile duct ligation induced liver fibrosis and achieved efficient inhibition of intracellular TGF-beta signaling, thereby counteracting profibrogenic effects in cultured HSC and in vivo. A direct link between the effect of alcohol and TGF-beta exists through reactive oxygen species that are generated in liver cells by alcohol metabolism and represent activators of TGF-beta signaling. Thus, soluble TbetaRII expression reduced experimental fibrogenesis in vitro and in vivo partially by decreasing intracellular ROS and inhibiting NADH oxidase. Approaches that specifically target profibrogenic TGF-beta signaling are promising to treat alcoholic liver disease in the future. However, to ensure safety for the patients to be treated, approaches with strong specificity need to be established. Therefore, it is essential to delineate the profibrogenic actions of TGF-beta and the influence of alcohol abuse in molecular detail.
Alcohol-induced diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the precise pathophysiological mechanisms are still largely unknown. Alcohol research depends essentially on animal models due to the fact that controlled experimental studies of ethanol-induced diseases in humans are unethical. Animal models have already been successfully applied to disclose and analyze molecular mechanisms in alcohol-induced diseases, partially by using knockout technology. Because of a lack of transferability of some animal models to the human condition, results have to be interpreted cautiously. For some alcohol-related diseases like chronic alcoholic pancreatitis, the ideal animal model does not yet exist. Here we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the findings based on animal models as well as the current concepts of pathophysiological mechanisms involved in acute and chronic alcoholic damage of the esophagus, stomach, small and large intestine, pancreas and liver.
We study the field dependence of the entanglement of formation in anisotropic S=1/2 antiferromagnetic chains displaying a T=0 field-driven quantum phase transition. The analysis is carried out via quantum Monte Carlo simulations. At zero temperature the entanglement estimators show abrupt changes at and around criticality, vanishing below the critical field, in correspondence with an exactly factorized state, and then immediately recovering a finite value upon passing through the quantum phase transition. At the quantum-critical point, a deep minimum in the pairwise-to-global entanglement ratio shows that multispin entanglement is strongly enhanced; moreover this signature represents a novel way of detecting the quantum phase transition of the system, relying entirely on entanglement estimators.
Interleukin-18 (IL-18), a recently described cytokine secreted mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. The purpose of this study was to determine tissue expression and serum levels of IL-18 in head and neck squamous cell carcinoma (HNSCC) and to evaluate ethanol and endotoxin-driven cytokine secretion. In 24 patients with primary HNSCC and 28 healthy controls, PBMC were isolated and incubated with 50 mM ethanol, LPS (doses 25 ng/ml, 250 ng/ml, 2500 ng/ml) and both agents for 24 h. Levels of IL-18 in serum, and cell supernatants were analysed by capture ELISA, IL-18 tissue level by immunoblotting. Serum levels of IL-8, IL-10 and IL-12, IFN-gamma, and endotoxin plasma levels were also determined. Statistical analysis involved Welch t-test and Page's test for trend. The majority of patients with HNSCC had high concentrations of serum IL-18. The level of IL-18 in the sera of these patients had a mean level of 271.7 pg/ml, while the mean IL-18 serum level in healthy controls was 174,0 pg/ml (p<0.001). Levels of IL-10 and IL-12, IFN-gamma were not increased in patients. Endotoxin was not detectable in either group. LPS stimulated dose-dependently IL-18 secretion from PBMC of patients and controls in vitro (p<0.05). Incubation with ethanol alone did not affect basal IL-18 secretion, but ethanol reduced LPS-stimulated IL-18 secretion compared to LPS stimulation alone. The mRNA expression of IL-18 in unstimulated PBMC and the response of PBMC to ethanol and LPS was similar in patients and controls. Our data on elevated serum levels of IL-18 in the majority of HNSCC cancer patients, irrespective of its biological activity, suggest that serum IL-18 might be a candidate for a new marker for HNSCC. The pathways for IL-18 production and its mechanisms of action in patients with HNSCC remain to be determined. Understanding of the immunological pathways might offer new therapeutic options in head and neck cancer in the future.
The antiferromagnetic Heisenberg model is studied on a two-dimensional bipartite quasiperiodic lattice. Using the stochastic series expansion quantum Monte Carlo method, the distribution of local staggered magnetic moments is determined on finite square approximants with up to 1393 sites, and a nontrivial inhomogeneous ground state is found. A hierarchical structure in the values of the moments is observed which arises from the self-similarity of the quasiperiodic lattice. The computed spin structure factor shows antiferromagnetic modulations that can be measured in neutron scattering and nuclear magnetic resonance experiments. This generic model is a first step towards understanding magnetic quasicrystals such as the recently discovered Zn-Mg-Ho icosahedral structure.
Alcohol-related diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the mechanisms and pathophysiology underlying the effects of ethanol on the organs of the digestive tract are not yet completely understood. Animal models represent an essential tool for investigating alcohol-related diseases because they give researchers the opportunity to use methods that cannot be used in humans, such as knockout technology. However, there is still a need for new animal models resembling the human condition, since for some alcohol-related diseases such as chronic alcoholic pancreatitis, the ideal animal model does not yet exist. In this chapter, we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the current concepts of the pathophysiological mechanisms involved in acute and chronic alcoholic damage of the oesophagus, stomach, small and large intestine, pancreas and liver.
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent hereditary form of colorectal cancer and is caused by germline mutations in mismatch repair (MMR) genes. The majority of mutations occur in MLH1 and MSH2. We report hereby seven novel germline mutations in these two genes (five in MLH1 and two in MSH2). All mutations have been found in families fulfilling criteria of the Bethesda guidelines and four of which also fulfilled the Amsterdam criteria. We identified three insertions or deletions of 1 bp leading to premature stop codons (MLH1: c.341delC, c.1413-1414insA; MSH2: c.1119delG) and three nonsense mutations (MLH1: c.67G>T [E23X], c.436C>T [Q146X]; MSH2: c.1857T>G [Y619X]). The corresponding tumors showed a high level of microsatellite instability (MSI-H) and a complete loss of expression of the affected protein. In addition, a missense mutation in MLH1 was identified (c.1984A>C [T662P]). The respective tumor also showed a high level of microsatellite instability but a reduced, rather then lost, expression of the MLH1-protein. This missense mutation was not found in 107 healthy control individuals and in 54 HNPCC patients.