To bridge the gap between in vitro and pharmacokinetic assessment of bioequivalence, modification of the experimental setup with the use of Peak VesselsTM and the validation of dissolution specifications with virtual bioequivalence trials appear to be promising approaches. However, neither approach is currently foreseen by the harmonized ICH M9 BCS-based biowaiver guidance. The Ser/Thr protein phosphatase Ppz1 from Saccharomyces cerevisiae is the best characterized member of a family of enzymes only found in fungi. Ppz1 is regulated in vivo by two inhibitory subunits, Hal3 and Vhs3, which are moonlighting proteins also involved in the decarboxylation of the 4-phosphopantothenoylcysteine (PPC) intermediate required for coenzyme A biosynthesis. It has been reported that, when overexpressed, Ppz1 is the most toxic protein in yeast. However, the reasons for such toxicity have not been elucidated. Here we show that the detrimental effect of excessive Ppz1 expression is due to an increase in its phosphatase activity and not to a plausible down-titration of the PPC decarboxylase components. We have identified several genes encoding ribosomal proteins and ribosome assembly factors as mild high-copy suppressors of the toxic Ppz1 effect. Ppz1 binds to ribosomes engaged in translation and copurifies with diverse ribosomal proteins and translation factors. Ppz1 overexpression results in Gcn2-dependent increased phosphorylation of eIF2α at Ser-51. Consistently, deletion of GCN2 partially suppresses the growth defect of a Ppz1 overexpressing strain. We propose that the deleterious effects of Ppz1 overexpression are in part due to alteration in normal protein synthesis. The crystalline lens plays an important role in the pathophysiology of primary angle closure (PAC) and primary angle-closure glaucoma (PACG). The aging process is associated with a progressive enlargement of the lens, resulting in greater iridolenticular and iridotrabecular contact, which exacerbates both pupillary block and appositional angle closure, irrespective of the cataract status of the lens. Cataract surgery has been shown to widen the angle and reduce intraocular pressure in eyes with PAC or PACG. Recently, clear lens phacoemulsification has been suggested as a treatment modality in such eyes. We review the literature on clear lens extraction in eyes with angle closure and discuss its efficacy, safety, and indications. Although it is evident that clear lens extraction is beneficial in eyes with PAC and PACG, it is technically challenging and should be performed by experienced surgeons who not only master the procedure, but are also able to deal with potential complications. Since the follow-up of the reviewed studies is relatively short, long-term follow-up (> 10 years) of patients who undergo this procedure is needed to evaluate the safety and confirm the early benefits reported. Calorie-reduced diets to combat obesity do work, but they only work when one sticks to the diet and the - relatively small - weight loss usually is short-lived. It is argued that calorie-reduced diets should converge with enduring lifestyle changes the diet is just the start of a lifelong new eating pattern. Getting people to change their lifestyles forever could increase the amount of lost weight and prevent relapse. However, a real behavior change is difficult, especially when longstanding habits are involved and the change is intended for the rest of life. It is argued here that adherence to a new lifestyle is much easier if sabotaging cognitive processes are tackled. An overview is given of four studies into the effects of exposure to reduce appetitive responding to tempting food cues. A robust effect of exposure on the ad lib intake of exposed foods was found in all studies participants ate significantly less of exposed foods after exposure compared to control interventions but no generalization to non-exposed foods was found. The reduced food intake after exposure was associated with a violation of overeating expectancies. It is discussed that lifestyle interventions might benefit from techniques that are really able to change longstanding habits. Specifically, the violation of overeating expectancies during exposure seems to be critical for controlled eating and should therefore be part of lifestyle interventions for obesity. BACKGROUND The quantitative study of behavioral responses to visual stimuli provides crucial information about the computations executed by neural circuits.  https://www.selleckchem.com/products/necrostatin-1.html  Insects have long served as powerful model systems, either when walking on air suspended balls (spherical treadmill), or flying while glued to a needle (virtual flight arena). NEW METHOD Here we present detailed instructions for 3D-printing and assembly of arenas optimized for visually guided navigation, including codes for presenting both celestial and panorama cues. These modular arenas can be used either as virtual flight arenas, or as spherical treadmills and consist entirely of commercial and 3D-printed components placed in a temperature and humidity controlled environment. COMPARISON TO EXISTING METHOD(S) Previous assays often include a combination of rather cost-intensive and technically complex, custom-built mechanical, electronic, and software components. Implementation amounts to a major challenge when working in an academic environment without the support of a professional machine shop. RESULTS Robust optomotor responses are induced in flyingDrosophila by displaying moving stripes in a cylinder surrounding the magnetically tethered fly. Similarly, changes in flight heading are induced by presenting changes in the orientation of linearly polarized UV light presented from above. Finally, responses to moving patterns are induced when individual flies are walking on an air-suspended ball. CONCLUSION These modular assays allow for the investigation of a diverse combination navigational cues (sky and panorama) in both flying and walking flies. They can be used for the molecular dissection of neural circuitry in Drosophila and can easily be rescaled for accommodating other insects. BACKGROUND Implantation accuracy of electrodes during neurosurgical interventions is necessary to ensure safety and efficacy. Typically, metrics are computed by visual inspection which is tedious, prone to inter-/intra-observer variation, and difficult to replicate across sites. NEW METHOD We propose an automated approach for computing implantation metrics and investigate potential sources of error. We focus on accuracy metrics commonly reported in the literature to validate our approach against metrics computed manually including entry point (EP) and target point (TP) localisation errors and angle differences between planned and implanted trajectories in 15 patients with a total of 158 stereoelectroencephalography (SEEG) electrodes. We evaluate the effect of line-of-best-fit approaches, EP definition and lateral versus Euclidean distance on metrics to provide recommendations for reporting implantation accuracy metrics. RESULTS We found no bias between manual and automated approaches for calculating accuracy metrics with limits of agreement of ±1 mm and ±1°.