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Chu Lundgaard
Chu Lundgaard

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Measuring Phase-Amplitude Coupling Based on the Jensen-Shannon Divergence and Correlation Matrix.

Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.Drug repurposing and drug combination are two strategies that have been widely used to overcome the traditional development of new anticancer drugs. Several FDA-approved drugs for other indications have been tested and have demonstrated beneficial anticancer effects. In this connection, our research group recently reported that Tacrine, used to treat Alzheimer's Disease, inhibits the growth of breast cancer MCF-7 cells both alone and in combination with a reference drug. In this view, we have now coupled Tacrine with the model amphipathic cell-penetrating peptide (CPP) MAP, to ascertain whether coupling of the CPP might enhance the drug's antiproliferative properties. To this end, we synthesized MAP through solid-phase peptide synthesis, coupled it with Tacrine, and made a comparative evaluation of the parent drug, peptide, and the conjugate regarding their permeability across the blood-brain barrier (BBB), ability to inhibit acetylcholinesterase (AChE) in vitro, and antiproliferative activity on cancer cells. Both MAP and its Tacrine conjugate were highly toxic to MCF-7 and SH-SY5Y cells. In turn, BBB-permeability studies were inconclusive, and conjugation to the CPP led to a considerable loss of Tacrine function as an AChE inhibitor. Nonetheless, this work reinforces the potential of repurposing Tacrine for cancer and enhances the antiproliferative activity of this drug through its conjugation to a CPP.The effects of the geometry parameters of a ceramic cleaver on the morphology of ball and second bonded points were studied using an automatic wire bonder, push pull tester, scanning electron microscope, ceramic capillary with different geometric parameters and φ25.4 μmAg-5Au bonding alloy wire, etc. ZIETDFMK The result shows that when the inner hole diameter (IHD) of the ceramic capillary is 1.3 times the diameter of the alloy wire (33 μm), the neck morphology of the ball bonded point (first bonded point) meet the requirements. The neck of the ball bonded point appeared to fracture when the IHD is 26 μm; The neck of the ball bonded point appeared as an irregular shape when the IHD is 41 μm. When the inner cutting angle diameter (ICAD) is 64 μm, the size of the mashed ball diameter (MBD) is qualified. When the ICAD is 51 μm, the MBD is too large and mashed ball overflows the pad. When the ICAD is 76 μm, the ball bonded point is too high. When the inner cutting bevel angle (ICBA) is 100°, the MBD size meets the requirements of the pad. When the ICBA was reduced to 70°, the ball bonded point is eccentric. When the ICBA was increased to 120°, the MBD is too large and is connected to the adjacent pad contact. The size of the fish tail of the second bonded point (second bonded point) changed in the same direction as the tip diameter (TD) changes. When the TD is 178 μm, the fish tail shape is regular and symmetrical. When the working face angle (WFA) is 8° and the outer circular radius (OCR) is equal to the diameter of the alloy wire (25.4 μm), the fish tail shape is regular. When the WFA is higher than 11° or the OCR is higher than 30 μm, the fish tail will appear as virtual welding, and when the WFA is less than 4°, the fish tail of the second bonded point will break due to thinning. When the OCR is less than 20 μm, the fish tail of the second bonded point is too long and causes a short circuit.Professional athletes are expected to continuously improve their performance, and some might also use illegal methods-e.g., autologous blood doping (ABD)-to achieve improvements. This article applies a systematic literature review to investigate differences in the ABD methods and the related performance and blood parameters owing to different storage conditions-cryopreservation (CP) and cold storage (CS)-and different storage durations. The literature research resulted in 34 original articles. The majority of currently published studies employed CS during ABD. This contrasts to the applied storage technique in professional sports, which was mainly reported to be CP. The second outcome of the literature research revealed large differences in the storage durations applied, which were in the range of one day to 17 weeks between blood sampling and re-infusion, which might affect recovery of the red blood cell mass and thus performance outcome related to ABD. Data revealed that performance parameters were positively affected by ABD when a minimal storage duration of four weeks was adhered. This article identified a need for further research that reflect common ABD practice and its real effects on performance parameters, but also on related blood parameters in order to develop valid and reliable ABD detection methods.Biological membranes were originally described as a fluid mosaic with uniform distribution of proteins and lipids. Later, heterogeneous membrane areas were found in many membrane systems including cyanobacterial thylakoids. In fact, cyanobacterial pigment-protein complexes (photosystems, phycobilisomes) form a heterogeneous mosaic of thylakoid membrane microdomains (MDs) restricting protein mobility. The trafficking of membrane proteins is one of the key factors for long-term survival under stress conditions, for instance during exposure to photoinhibitory light conditions. However, the mobility of unbound 'free' proteins in thylakoid membrane is poorly characterized. In this work, we assessed the maximal diffusional ability of a small, unbound thylakoid membrane protein by semi-single molecule FCS (fluorescence correlation spectroscopy) method in the cyanobacterium Synechocystis sp. PCC6803. We utilized a GFP-tagged variant of the cytochrome b6f subunit PetC1 (PetC1-GFP), which was not assembled in the b6f complex due to the presence of the tag. Subsequent FCS measurements have identified a very fast diffusion of the PetC1-GFP protein in the thylakoid membrane (D = 0.14 - 2.95 µm2s-1). This means that the mobility of PetC1-GFP was comparable with that of free lipids and was 50-500 times higher in comparison to the mobility of proteins (e.g., IsiA, LHCII-light-harvesting complexes of PSII) naturally associated with larger thylakoid membrane complexes like photosystems. Our results thus demonstrate the ability of free thylakoid-membrane proteins to move very fast, revealing the crucial role of protein-protein interactions in the mobility restrictions for large thylakoid protein complexes.ZIETDFMK

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