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Hofstadter-Hubbard physics
(2020)
The Hofstadter model, besides the Haldane and Kane-Mele models, is the most common tight-binding model which hosts topologically nontrivial states of matter. In its time-reversal-symmetric formulation the model can even describe topological insulators. Experimentally, the Hofstadter model was realized with ultracold quantum gases in optical lattices which is a wellcontrolled way to engineer quantum states of tight-binding Hamiltonians. Another established control parameter in ultracold quantum gases are twoparticle, on-site interactions, also known as Hubbard interactions. This work aims at introducing the reader to the concepts of topological states of matter, a collection of corresponding tight-binding models, and the methodology to treat interacting topological states with dynamical mean-field theory.We present recent results for inhomogeneous, interacting systems, spinimbalanced magnetic systems, propose experimental detection methods, and extensions to three-dimensional topological states.
Objective: Children with pre-school asthma suffer disproportionally more often from severe asthma exacerbations with emergency visits and hospital admissions compared to school children. Despite this high disease burden, there are only a few reports looking at this particular severe asthma cohort. Similarly, there is little real-life research on the distribution of asthma phenotypes and personalized treatment at discharge in this age group. Patients and Methods: Retrospective analysis of the electronic charts of all children aged 1–5 years with asthma hospitalizations (ICD J45) at the Frankfurt University between 2008 and 2017. An acute severe asthma exacerbation was defined as dyspnea, oxygen demand, and/or systemic steroid therapy. Age, gender, duration of hospitalization, asthma phenotype, treatment, and readmission rate were analyzed. Results: Of 572 patients, 205 met the definition of acute severe asthma. The phenotypic characterization showed 56.1% had allergic asthma, 15.2% eosinophilic asthma and 28.7% non-allergic asthma. Of these patients, 71.7% were discharged with inhaled corticosteroids (ICS) or ICS + long-acting-beta-agonists (LABA), 15.1% with leukotriene antagonists (LTRA) and 7.3% salbutamol on demand. The rate of emergency presentations (emergency department and readmission) within 12 months after discharge was high (n = 42; 20.5%). No phenotype tailored treatment was detectable. Neither the number of eosinophils (>300/μl) nor the treatment at discharge had an effect on emergency visits and readmission rate. Conclusion: Despite protective therapy with ICS, ICS + LABA, or LTRA, the readmission rate was high. Thus, current care and treatment strategies should be reevaluated continuously, in order to better control asthma in pre-school children and prevent hospitalization.
This study examined age‐related differences in the effectiveness of two generative learning strategies (GLSs). Twenty‐five children aged 9–11 and 25 university students aged 17–29 performed a facts learning task in which they had to generate either a prediction or an example before seeing the correct result. We found a significant Age × Learning Strategy interaction, with children remembering more facts after generating predictions rather than examples, whereas both strategies were similarly effective in adults. Pupillary data indicated that predictions stimulated surprise, whereas the effectiveness of example‐based learning correlated with children’s analogical reasoning abilities. These findings suggest that there are different cognitive prerequisites for different GLSs, which results in varying degrees of strategy effectiveness by age.
Photochemical internalization (PCI) is a technology to induce a localized, intracellular enhancement of therapeutics that are processed through endosomal pathways, including gemcitabine in malignant cells. In addition to a direct phototoxic and tumoricidal effect, PCI specifically disrupts endosomal membranes and, thereby, the compartmentalization of certain cytotoxic compounds to enhance a drug’s intended intracellular target reach within the tissue treated.
Non-resectable extrahepatic cholangiocarcinoma (eCCA) is a common primary tumor and gemcitabine/cisplatin chemotherapy is widely considered standard of care for it. PCI is well suited as an endoscopic intervention, and clinical observations in three subjects participating in a phase I/IIa dose escalation safety trial are described. The trial included patients with perihilar, non-resectable CCA suitable for standard-of-care chemotherapy. Per protocol, a single endoscopic PCI procedure with gemcitabine was conducted at the initiation of standard gemcitabine/cisplatin therapy. Sixteen patients enrolled in the initial dose escalation phase of the trial, which later was extended to explore the safety of a second PCI procedure during chemotherapy.
While limited to a case series, the various clinical observations described here serve to illustrate the effects of localized, perihilar tumor targeting in appropriate patients by any safe methodology, including PCI. As previously indicated by clinical data using other localized treatment modalities, adding a directed, tumor-targeting treatment to systemic therapy to ameliorate the progressively expanding extrahepatic tumor burden can have important effects on the overall outcome of systemic treatment in many patients who have incurable eCCA.
A novel, broad-acting peptide inhibitor of double-stranded DNA virus gene expression and replication
(2020)
Viral infections are a global disease burden with only a limited number of antiviral agents available. Due to newly emerging viral pathogens and increasing occurrence of drug resistance, there is a continuous need for additional therapeutic options, preferably with extended target range. In the present study, we describe a novel antiviral peptide with broad activity against several double-stranded DNA viruses. The 22-mer peptide TAT-I24 potently neutralized viruses such as herpes simplex viruses, adenovirus type 5, cytomegalovirus, vaccinia virus, and simian virus 40 in cell culture models, while being less active against RNA viruses. The peptide TAT-I24 therefore represents a novel and promising drug candidate for use against double-stranded DNA viruses.
Particulate autogenous tooth roots are used for alveolar bone augmentation surgery; however, dental plaque may provoke an inflammatory response that may counteract the desired graft consolidation process. Traditional mechanical cleaning of extracted teeth may be of support to lower a possible inflammatory response of the autograft. To test this assumption, extracted porcine teeth were left either uncleaned or underwent mechanical cleaning with a toothbrush and toothpaste before being fragmented and subjected to acid lysis, termed as unclean acid dentine lysate (ucADL) and clean acid dentine lysate (cADL), respectively. The inflammatory responses of murine macrophage RAW 264.7 cells being exposed to the respective acid dentine lysates were evaluated at the level of inflammatory gene expression and IL6 immunoassays. We report here that acid lysates obtained from uncleaned teeth provoked a robust increase in IL1β, IL6, and COX2 in RAW 264.7 cells. The mechanical removal of dental plaque significantly reduced the inflammatory response. Consistently, Limulus tests revealed that tooth cleaning lowers the presence of endotoxins in dentine lysates. To further prove the involvement of endotoxins, a toll-like receptor 4 (TLR4) inhibitor TAK242 was introduced. TAK242 abolished the inflammatory response provoked by acid lysates obtained from uncleaned teeth in RAW 264.7 cells. Moreover, nuclear translocation and phosphorylation of the TLR4 downstream NFκB-p65 were attenuated at the presence of cleaned versus uncleaned dentine lysates. Taken together, our data support the importance of dental plaque removal of teeth being extracted for alveolar bone augmentation surgery.
We extend the parton‐hadron‐string dynamics (PHSD) transport approach in the partonic sector by explicitly calculating the total and differential partonic scattering cross sections as a function of temperature T and baryon chemical potential μB on the basis of the effective propagators and couplings from the dynamical quasiparticle model (DQPM) that is matched to reproduce the equation of state of the partonic system above the deconfinement temperature Tc from lattice quantum chromodynamics (QCD). We calculate the collisional widths for the partonic degrees of freedom at finite T and μB in the time‐like sector and conclude that the quasiparticle limit holds sufficiently well. Furthermore, the ratio of shear viscosity η over entropy density s, that is, η/s, is evaluated using the collisional widths and compared to lattice QCD(lQCD) calculations for μB = 0 as well. We find that the ratio η/s does not differ very much from that calculated within the original DQPM on the basis of the Kubo formalism. Furthermore, there is only a very modest change of η/s with the baryon chemical μB as a function of the scaled temperature T/Tc(μB). This also holds for a variety of hadronic observables from central A + A collisions in the energy range 5 GeV urn:x-wiley:00046337:media:asna201913708:asna201913708-math-0001 200 GeV when implementing the differential cross sections into the PHSD approach. Accordingly, it will be difficult to extract finite μB signals from the partonic dynamics based on “bulk” observables.
Volatility clustering and fat tails are prominently observed in financial markets. Here, we analyze the underlying mechanisms of three agent-based models explaining these stylized facts in terms of market instabilities and compare them on empirical grounds. To this end, we first develop a general framework for detecting tail events in stock markets. In particular, we introduce Hawkes processes to automatically identify and date onsets of market turmoils which result in increased volatility. Second, we introduce three different indicators to predict those onsets. Each of the three indicators is derived from and tailored to one of the models, namely quantifying information content, critical slowing down or market risk perception. Finally, we apply our indicators to simulated and real market data. We find that all indicators reliably predict market events on simulated data and clearly distinguish the different models. In contrast, a systematic comparison on the stocks of the Forbes 500 companies shows a markedly lower performance. Overall, predicting the onset of market turmoils appears difficult, yet, over very short time horizons high or rising volatility exhibits some predictive power.
A realistic simulation of the atmospheric boundary layer (ABL) depends on an accurate representation of the land–atmosphere coupling. Land surface temperature (LST) plays an important role in this context and the assimilation of LST can lead to improved estimates of the boundary layer and its processes. We assimilated synthetic satellite LST retrievals derived from a nature run as truth into a fully coupled, state‐of‐the‐art land–atmosphere numeric weather prediction model. As assimilation system a local ensemble transform Kalman filter was used and the control vector was augmented by the soil temperature and humidity. To evaluate the concept of the augmented control vector, two‐day case‐studies with different control vector settings were conducted for clear‐sky periods in March and August 2017. These experiments with hourly LST assimilation were validated against the nature run and overall, the RMSE of atmospheric and soil temperature of the first‐guess (and analysis) were reduced. The temperature estimate of the ABL was particularly improved during daytime as was the estimate of the soil temperature during the whole diurnal cycle. The best impact of LST assimilation on the soil and the ABL was achieved with the augmented control vector. Through the coupling between the soil and the atmosphere, the assimilation of LST can have a positive impact on the temperature forecast of the ABL even after 15 hr because of the memory of the soil. These encouraging results motivate further work towards the assimilation of real satellite LST retrievals.