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This study investigated the projected changes in the annual mean surface air temperature (SAT) over China under the 1.5 and 2.0?°C targets, by analyzing the outputs from 22 models of the Coupled Model Intercomparison Project Phas...
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This study investigated the projected changes in the annual mean surface air temperature (SAT) over China under the 1.5 and 2.0?°C targets, by analyzing the outputs from 22 models of the Coupled Model Intercomparison Project Phase 5. Under the 1.5?°C target, the scope of changes in the average SAT over China is quite narrow and has the largest probability to increase by 1.7–2.0?°C under the various RCP pathways, although the time of occurrence of the 1.5?°C target has a large spread of 40–60 years. Similarly, the models consistently show that the average SAT over China would most likely increase by 2.4–2.7?°C under the 2.0?°C target. Furthermore, the warming shows a clear spatial distinction over China: being stronger in the northwest part and weaker in the southeast part. Under all RCP pathways, the SAT over the northwest part would increase by 1.9–2.1?°C for the 1.5?°C target, which is much stronger than the SAT increase over the southeast part (1.3–1.5?°C). A similar spatial pattern appears for the 2.0?°C target.
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Phosphoinositide-specific phospholipase C (PI-PLC) belongs to an important class of enzymes involved in signaling related to lipids. They hydrolyze a membrane-associated phospholipid, phosphatidylinositol-4,5-bisphosphate, to prod...
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Phosphoinositide-specific phospholipase C (PI-PLC) belongs to an important class of enzymes involved in signaling related to lipids. They hydrolyze a membrane-associated phospholipid, phosphatidylinositol-4,5-bisphosphate, to produce inositol-1,4,5-trisphosphate and diacylglycerol. The role of PI-PLC and the mechanism behind its functioning is well studied in animal system; however, mechanism of plant PI-PLC functioning remains largely obscure. Here, we attempted to summarize the understanding regarding plant PI-PLC mechanism of regulation, localization, and domain association. Using sedimentation based phospholipid binding assay and surface plasmon resonance spectroscopy, it was demonstrated that C2 domain of plant PI-PLC alone is capable of targeting membranes. Moreover, change in surface hydrophobicity upon calcium stimulus is the key element in targeting plant PI-PLC from soluble fractions to membranes. This property of altering surface hydrophobicity plays a pivot role in regulation of PI-PLC activity.
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摘要 :
Phosphoinositide-specific phospholipase C (PI-PLC) belongs to an important class of enzymes involved in signaling related to lipids. They hydrolyze a membrane-associated phospholipid, phosphatidylinositol-4,5-bisphosphate, to prod...
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Phosphoinositide-specific phospholipase C (PI-PLC) belongs to an important class of enzymes involved in signaling related to lipids. They hydrolyze a membrane-associated phospholipid, phosphatidylinositol-4,5-bisphosphate, to produce inositol-1,4,5-trisphosphate and diacylglycerol. The role of PI-PLC and the mechanism behind its functioning is well studied in animal system; however, mechanism of plant PI-PLC functioning remains largely obscure. Here, we attempted to summarize the understanding regarding plant PI-PLC mechanism of regulation, localization, and domain association. Using sedimentation based phospholipid binding assay and surface plasmon resonance spectroscopy, it was demonstrated that C2 domain of plant PI-PLC alone is capable of targeting membranes. Moreover, change in surface hydrophobicity upon calcium stimulus is the key element in targeting plant PI-PLC from soluble fractions to membranes. This property of altering surface hydrophobicity plays a pivot role in regulation of PI-PLC activity.
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This study investigates changes in the East Asian winter monsoon (EAWM) under 1.5 and 2.0 degrees C global warming (1.5 and 2.0GW) targets using multi-model results from the Coupled Model Intercomparison Project phase 5 (CMIP5). I...
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This study investigates changes in the East Asian winter monsoon (EAWM) under 1.5 and 2.0 degrees C global warming (1.5 and 2.0GW) targets using multi-model results from the Coupled Model Intercomparison Project phase 5 (CMIP5). It is found that the surface air temperature increases over the Asian continent and Pacific, and the precipitation increases over the northern Asian continent in winter during the 1.5 and 2.0GW periods. For the 1.5GW period, large uncertainties can be found in the projection of EAWM system members (i.e., Siberian high, Aleutian low, low-level winds over eastern Asia, East Asian trough [EAT] and East Asian jet stream [EAJS]). For the 2.0GW period, more than two-thirds of the models show that the Siberian high, the EAT and the meridional shear of the EAJS are weakened, but the Aleutian low is intensified. In addition, the intensified Aleutian low enhances low-level northwesterly wind along the coast of northeastern Asia. Compared to those in the 1.5GW period, the EAWM system members show more robust changes during the 2.0GW period, except for the low-level winds at mid-latitude eastern Asia. These conclusions are suitable for both the RCP4.5 and RCP8.5 scenarios.
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MYC oncogene is involved in the majority of human cancers and is often associated with poor outcomes, rendering it an extraordinarily desirable target, but therapeutic targeting of c‐Myc protein has been a challenge for >30 years...
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MYC oncogene is involved in the majority of human cancers and is often associated with poor outcomes, rendering it an extraordinarily desirable target, but therapeutic targeting of c‐Myc protein has been a challenge for >30 years. Here, WBC100, a novel oral active molecule glue that selectively degrades c‐Myc protein over other proteins and potently kills c‐Myc overexpressing cancer cells is reported. WBC100 targets the nuclear localization signal 1 (NLS1)–Basic–nuclear localization signal 2 (NLS2) region of c‐Myc and induces c‐Myc protein degradation through ubiquitin E3 ligase CHIP mediated 26S proteasome pathway, leading to apoptosis of cancer cells. In vivo, WBC100 potently regresses multiple lethal c‐Myc overexpressing tumors such as acute myeloid leukemia, pancreatic, and gastric cancers with good tolerability in multiple xenograft mouse models. Identification of the NLS1–Basic–NLS2 region as a druggable pocket for targeting the “undruggable” c‐Myc protein and that single‐agent WBC100 potently regresses c‐Myc overexpressing tumors through selective c‐Myc proteolysis opens new perspectives for pharmacologically intervening c‐Myc in human cancers.
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Gas target systems have been used for decades on cyclotrons to produce radionuclides for medical imaging. However, the activity recovered from such targets is often lower than its theoretically predicted value. Past research has s...
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Gas target systems have been used for decades on cyclotrons to produce radionuclides for medical imaging. However, the activity recovered from such targets is often lower than its theoretically predicted value. Past research has suggested that nuclide interactions with the walls of the target body may play a key role in the loss of recoverable radionuclide activity. Here, we consider gas targets and modify the standard radionuclide production equation by adding a loss term representing radionuclides depositing on the walls of the target. We derive the form of the deposition term based on a simple adsorption model which is then linearized by solving for leading order terms. The resulting production equation uses one fitting parameter to give an estimate of the recoverable activity produced in a target system, taking adsorption into account. The model is then fit to six data series, taken in-house and reported in the literature and a parity plot compares model predictions to experimental data. The model is able to better track the data than any previous models, and points towards a phenomenological understanding of adsorption in target systems.
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Tumor growth and metastasis are dependent on angiogenesis. The overexpression of integrin alpha(v)beta(3) on angiogenic vessels and on numerous malignant human tumor cells suggests that these labeled ligands of integrin are potent...
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Tumor growth and metastasis are dependent on angiogenesis. The overexpression of integrin alpha(v)beta(3) on angiogenic vessels and on numerous malignant human tumor cells suggests that these labeled ligands of integrin are potentially suitable for molecular imaging and in targeted therapy of tumors. In previous studies, we added a beta-lactamase variant with reduced immunogenicity to the cyclic peptide RGD4C, resulting in the fusion protein RGD4C beta L, which is suitable for use in targeted enzyme prodrug therapy (TEPT), a promising treatment for tumors. The targeting of the aforementioned fusion protein serves an important role in TEPT. In the present study, RGD4C beta L was labeled with I-125 and the targeting effect on integrin-positive tumors was evaluated. The results demonstrated that the I-125-RGD4C beta L protein exhibited high levels of accumulation at the tumor site and rapid renal clearance, which revealed the potency and efficiency of RGD4C beta L in TEPT.
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Abstract The 3C protease (3C Pro) plays a significant role in the life cycle of picornaviruses from replication to translation, making it an attractive target for structure‐based design of drugs against picornaviruses. The struct...
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Abstract The 3C protease (3C Pro) plays a significant role in the life cycle of picornaviruses from replication to translation, making it an attractive target for structure‐based design of drugs against picornaviruses. The structurally related 3C‐like protease (3CL Pro) is an important protein involved in the replication of coronaviruses. With the emergence of COVID‐19 and consequent intensive research into 3CL Pro, development of 3CL Pro inhibitors has emerged as a popular topic. This article compares the similarities of the target pockets of various 3C and 3CL Pros from numerous pathogenic viruses. This article also reports several types of 3C Pro inhibitors that are currently undergoing extensive studies and introduces various structural modifications of 3C Pro inhibitors to provide a reference for the development of new and more effective inhibitors of 3C Pro and 3CL Pro.
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A tandem target for the simultaneous production of [~(18)F]-fluoride and [~(11)C]CH_4 with 18 MeV protons has been manufactured and evaluated. Tungsten was chosen as a grid material because of its good mechanical and thermal prope...
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A tandem target for the simultaneous production of [~(18)F]-fluoride and [~(11)C]CH_4 with 18 MeV protons has been manufactured and evaluated. Tungsten was chosen as a grid material because of its good mechanical and thermal properties. Four tungsten grids were placed between the liquid target cavities and between the air cooling units. This tandem target system showed a stable production yield and thus appears to be suitable for a routine production of [~(18)F]-fluoride and [~(11)C]CH_4 with 18 MeV protons.
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