Therapeutic hypothermia (TH) is a powerful neuroprotective strategy that has provided robust evidence for neuroprotection in pre-clinical studies of neurological disorders. Despite strong pre-clinical evidence, TH has not shown efficacy in clinical trials of most neurological disorders. The only successful trials employing therapeutic hypothermia were related to cardiac arrest in adults and hypoxic ischemic injury in neonates. Further investigations into the parameters of its use, and study design comparisons between pre-clinical and clinical studies, are warranted. This article demonstrates two methods of short-duration hypothermia induction. The first method allows for rapid hypothermia induction in rats using ethanol spray and fans. This method works by cooling the skin, which has been less commonly used in clinical trials and may have different physiological effects. Cooling is much more rapid with this technique than is achievable in human patients due to differences in surface area to volume ratio. Along with this, a second method is also presented, which allows for a clinically achievable cooling rate for short-duration hypothermia. https://www.selleckchem.com/products/bms309403.html This method is easy to implement, reproducible and does not require active skin cooling.Organoids provide a promising platform to study disease mechanism and treatments, directly in the context of human tissue with the versatility and throughput of cell culture. Mature human retinal organoids are utilized to screen potential pharmaceutical treatments for the age-related retinal degenerative disease macular telangiectasia type 2 (MacTel). We have recently shown that MacTel can be caused by elevated levels of an atypical lipid species, deoxysphingolipids (deoxySLs). These lipids are toxic to the retina and may drive the photoreceptor loss that occurs in MacTel patients. To screen drugs for their ability to prevent deoxySL photoreceptor toxicity, we generated human retinal organoids from a non-MacTel induced pluripotent stem cell (iPSC) line and matured them to a post-mitotic age where they develop all of the neuronal lineage-derived cells of the retina, including functionally mature photoreceptors. The retinal organoids were treated with a deoxySL metabolite and apoptosis was measured within the photoreceptor layer using immunohistochemistry. Using this toxicity model, pharmacological compounds that prevent deoxySL-induced photoreceptor death were screened. Using a targeted candidate approach, we determined that fenofibrate, a drug commonly prescribed for the treatment of high cholesterol and triglycerides, can also prevent deoxySL toxicity in the cells of the retina. The toxicity screen successfully identified an FDA-approved drug that can prevent photoreceptor death. This is a directly actionable finding owing to the highly disease-relevant model tested. This platform can be easily modified to test any number of metabolic stressors and potential pharmacological interventions for future treatment discovery in retinal diseases.We present an in-house, in situ Grazing Incidence Small Angle X-ray Scattering (GISAXS) experiment, developed to probe the drying kinetics of roll-to-roll slot-die coating of the active layer in organic photovoltaics (OPVs), during deposition. For this demonstration, the focus is on the combination of P3HTO-IDTBR and P3HTEH-IDTBR, which have different drying kinetics and device performance, despite their chemical structure only varying slightly by the sidechain of the small molecule acceptor. This article provides a step-by-step guide to perform an in situ GISAXS experiment and demonstrates how to analyze and interpret the results. Usually, performing this type of in situ X-ray experiments to investigate the drying kinetics of the active layer in OPVs relies on access to synchrotrons. However, by using and further developing the method described in this paper, it is possible to perform experiments with a coarse temporal and spatial resolution, on a day-to-day basis to gain fundamental insight in the morphology of drying inks.Bones are one of the most common sites of cancer metastasis, which usually causes pain and impairs quality of life. Radiation therapy combined with opioids is the standard treatment for painful bone metastases. This treatment achieves effective pain control in 60-74% of patients, but limited treatment choices with limited benefits are available for recurrent or residual painful bone metastases after radiotherapy. More than 40% of patients still experience moderate to severe bone pain after reirradiation. Magnetic resonance-guided focused ultrasound (MRgFUS) combines high-intensity focused ultrasound, which achieves thermal ablation of bone metastases and subsequent pain reduction, with real-time magnetic resonance (MR) thermometry to monitor the temperature of anatomic MR images, with an accuracy of 1 °C, spatial resolution of 1 mm, and temporal resolution within 3 s. As well as being increasingly used clinically for controlling metastatic bone pain, the use of MRgFUS for other diseases has also been tested. However, the use of MR software as a thermometer is the only technique available to verify the accuracy of the software and assure energy delivery. Here, we describe an efficient method of quality assurance we developed for thermal detection and energy delivery before each MRgFUS treatment and also propose a modified workflow to expedite the treatment course as well as to reduce patients' pain during the procedure.Membrane proteins are vital for cell function and thus represent important drug targets. Solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy offers a unique access to probe the structure and dynamics of such proteins in biological membranes of increasing complexity. Here, we present modern solid-state NMR spectroscopy as a tool to study structure and dynamics of proteins in natural lipid membranes and at atomic scale. Such spectroscopic studies profit from the use of high-sensitivity ssNMR methods, i.e., proton-(1H)-detected ssNMR and DNP (Dynamic Nuclear Polarization) supported ssNMR. Using bacterial outer membrane beta-barrel protein BamA and the ion channel KcsA, we present methods to prepare isotope-labeled membrane proteins and to derive structural and motional information by ssNMR.