Effects of GPR139 agonism on effort expenditure for food reward in rodent models: Evidence for pro-motivational actions

Apathy, deficiency of motivation including willingness to exert effort for reward, is a common symptom in many psychiatric and neurological disorders, including depression and schizophrenia. Despite improved understanding of the neurocircuitry and neurochemistry underlying normal and deficient motivation, there is still no approved pharmacological treatment for such a deficiency. GPR139 is an orphan G protein-coupled receptor expressed in brain regions which contribute to the neural circuitry that controls motivation including effortful responding for reward, typically sweet gustatory reward. The GPR139 agonist TAK-041 is currently under development for treatment of negative symptoms in schizophrenia which include apathy. To date, however, there are no published preclinical data regarding its potential effect on reward motivation or deficiencies thereof. Here we report in vitro evidence confirming that TAK-041 increases intracellular Ca2+ mobilization and has high selectivity for GPR139. In vivo, TAK-041 was brain penetrant and showed a favorable pharmacokinetic profile. It was without effect on extracellular dopamine concentration in the nucleus accumbens. In addition, TAK-041 did not alter the effort exerted to obtain sweet gustatory reward in rats that were moderately food deprived. By contrast, TAK-041 increased the effort exerted to obtain sweet gustatory reward in mice that were only minimally food deprived; furthermore, this effect of TAK-041 occurred both in control mice and in mice in which deficient effortful responding was induced by chronic social stress. Overall, this study provides preclinical evidence in support of GPR139 agonism as a molecular target mechanism for treatment of apathy

Comparative Study between Direct and Pseudomorphic Transformation of Rice Husk Ash into MFI-Type Zeolite

Pre-shaped mesoporous amorphous rice husk ash (RHA) and MCM-41 derived from RHA as a silica source were transformed into MFI-type zeolites using two different structure-directing agents. Tetrapropylammonium hydroxide (TPAOH) was utilized as an alkali source for silica dissolution and structure control during the direct transformation of RHA into zeolite. A monopropylamine (PA)-containing alkaline solution (NaOH) was used for the pseudomorphic transformation of RHA or MCM-41 into zeolite. The hydrothermal conversion of RHA or MCM-41 into MFI-type zeolites was investigated as a function of reaction time at 175 °C. With PA as template, the crystallization took place inside and on the outer surface of RHA or MCM-41 without losing the original shape of the initial silica sources, while TPAOH led to the formation of conventional MFI-type zeolite crystals due to the complete dissolution of RHA. The final products were characterized by X-ray diffraction, nitrogen adsorption, scanning electron microscopy, and optical emission spectroscopy

Comparative Study between Direct and Pseudomorphic Transformation of Rice Husk Ash into MFI-Type Zeolite

Pre-shaped mesoporous amorphous rice husk ash (RHA) and MCM-41 derived from RHA as a silica source were transformed into MFI-type zeolites using two different structure-directing agents. Tetrapropylammonium hydroxide (TPAOH) was utilized as an alkali source for silica dissolution and structure control during the direct transformation of RHA into zeolite. A monopropylamine (PA)-containing alkaline solution (NaOH) was used for the pseudomorphic transformation of RHA or MCM-41 into zeolite. The hydrothermal conversion of RHA or MCM-41 into MFI-type zeolites was investigated as a function of reaction time at 175 °C. With PA as template, the crystallization took place inside and on the outer surface of RHA or MCM-41 without losing the original shape of the initial silica sources, while TPAOH led to the formation of conventional MFI-type zeolite crystals due to the complete dissolution of RHA. The final products were characterized by X-ray diffraction, nitrogen adsorption, scanning electron microscopy, and optical emission spectroscopy

Does the Duration of Primary and First Revision Surgery Influence the Probability of First and Subsequent Implant Failures after Extremity Sarcoma Resection and Megaprosthetic Reconstruction?

Complications in megaprosthetic reconstruction following sarcoma resection are quite common. While several risk factors for failure have been explored, there is a scarcity of studies investigating the effect of the duration of surgery. We performed a retrospective study of 568 sarcoma patients that underwent megaprosthetic reconstruction between 1993 and 2015. Differences in the length of surgery and implant survival were assessed with the Kaplan–Meier method, the log-rank test and multivariate Cox regressions using an optimal cut-off value determined by receiver operating curves analysis using Youden’s index. 230 patients developed a first and 112 patients a subsequent prosthetic failure. The median duration of initial surgery was 210 min. Patients who developed a first failure had a longer duration of the initial surgery (225 vs. 205 min, p = 0.0001). There were no differences in the probability of infection between patients with longer and shorter duration of initial surgery (12% vs. 13% at 5 years, p = 0.492); however, the probability of mechanical failure was higher in patients with longer initial surgery (38% vs. 23% at 5 years, p = 0.006). The median length of revision surgery for the first megaprosthetic failure was 101 min. Patients who underwent first revision for infection and did not develop a second failure had a longer median duration of the first revision surgery (150 min vs. 120 min, p = 0.016). A shorter length of the initial surgery appears beneficial, however, the notion that longer operating time increases the risk of deep infection could not be reproduced in our study. In revision surgery for infection, a longer operating time, possibly indicating a more thorough debridement, appears to be associated with a lower risk for subsequent revision

Artificial Intelligence in Public Discourse

This book contains 26 studies conducted by students in the Cognitive Science seminar "Artificial Intelligence in Public Discourse". In their studies, they explore the use of the term Artificial Intelligence (AI) and related subfields in various parts of public discourse such as Twitter, user comments on news sites, expert interviews, government documents, television shows, newspapers, etc. It is investigated which strengths, weaknesses, opportunities, and threats are ascribed to AI technology and how this relates to the technical and academic state of the art and discussion. Most studies employ qualitative methods, but quantitative and mixed-methods approaches are also used