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A pooled overall survival analysis at
2022-05-16
A pooled overall survival analysis at 1year showed no difference in survival between the two study arms, although these studies were not designed or powered to demonstrate a survival benefit. Among the 979 total patients in both ROMANA 1 and 2, about 55% continued on to the ROMANA 3 trial. That tria
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Based upon the present findings it
2022-05-16
Based upon the present findings, it is tempting to imagine that selective, and especially stable blood–brain barrier (BBB) penetrating GalR1 antagonists might be useful as drugs for acute suppression of appetite. While this may be possible, previous studies using nonspecific galanin antagonists yiel
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Comparison of dlGALRs deduced amino acid sequences with that
2022-05-16
Comparison of dlGALRs deduced amino NGB 2904 sequences with that of human GALRs demonstrate that the GALR1 ortholog sequences have diverged less than those of GALR2. Since often duplicate genes undergo divergent evolution through sub-functionalization, loss or gain of new functions (Prince and Picke
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Herein we describe the design and optimization of
2022-05-16
Herein, we describe the design and optimization of fused-ring phenyl propanoic acids as novel GPR40 agonists, leading to the discovery of compound 40a which exhibits excellent pharmacokinetic properties, improved hepatobiliary transporter inhibition, and significant glucose-lowering efficacy during
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In spite of decades of research the mechanisms of
2022-05-16
In spite of decades of research the mechanisms of SV endocytosis and recycling remain controversial. Accumulating evidence suggests that SV endocytosis occurs by more than one mechanism (e.g. clathrin-independent endocytosis, clathrin-mediated endocytosis, bulk endocytosis; reviewed in (Dittman and
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Evidence suggests that phosphorylation increases
2022-05-16
Evidence suggests that phosphorylation increases synaptotagmin affinity for the SNARE complex [15], [128]. It is, however, unclear how this might affect release. Synaptotagmin has been identified as part of the minimal vesicle docking machinery in chromaffin STF 31 receptor [129]. Thus, phosphoryla
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There are limited studies on antibody responses
2022-05-16
There are limited studies on antibody responses against HIV-1 integrase antigen. According to previous studies, almost 5 percent of individuals infected with HIV never raise anti-integrase TC-E 5003 (Rikhtegaran Tehrani et al., 2015; Chang et al., 1985). If this rate is identical in individuals inf
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br Methods br Results and
2022-05-13
Methods Results and discussion Conclusions In this work, 100-ns MDSs were applied on the WT and on the R155K and D168A single point mutations of the NS3/4A protease in the apo form and in complex with ASV, a current drug in phase III clinical trials. According to the PCA, these two mutation
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In order to determine which complex
2022-05-13
In order to determine which complex of the electron transport chain is targeted by Authipyrin, a semi-intact assay was performed. The substrates of each complex were added separately in combination with Authipyrin or the respective control inhibitor. Seahorse XF plasma membrane permeabilizer (PMP) w
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br Materials and methods br Results
2022-05-13
Materials and methods Results Discussion ENU mutagenesis is a powerful approach to identify novel genes or ampk inhibitors to dissect the molecular basis of mammalian immune system (Siggs, 2014). T cells are critical components in the host defense against pathogens, and their activity has t
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To this end we evaluated
2022-05-13
To this end, we evaluated novel D22 analogs for selectivity to inhibit substrate transport in OCT2, OCT3, and PMAT heterologous cell CORM-3 systems, and in mouse hippocampal and striatal preparations. Chosen analogs were based upon availability of essential chemical precursors (e.g. 6-substituted-2-
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Ca independent release of L C glutamate and GABA
2022-05-13
Ca2+-independent release of L-[14C]glutamate and [3Н]GABA that occurs via transporters working in the reverse mode also insignificantly increased in vitamin D3 deficiency despite decreased GAT-3 and EAAC-1 TAK-875 and neurotransmitter uptake efficacy Fig. 3, Fig. 6 A). However, the upward tendency i
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The ion conduction pathway reported herein accounts for all
2022-05-13
The ion conduction pathway reported herein accounts for all known functional properties of EAAT/GltPh anion channels. Simulations reveal unitary current amplitudes and ion selectivities (Figures 3C and 3D) that resemble experimental results (Melzer et al., 2003, Wadiche and Kavanaugh, 1998). The cal
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It is increasingly argued that the immunosuppressive effects
2022-05-13
It is increasingly argued that the immunosuppressive effects of GCs are conferred indirectly by GR through the activation of genes encoding proteins that inhibit ppy of proinflammatory genes 86, 87, 88. Genomic studies offer another mechanism compatible with the idea that GC-mediated repression is
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The findings in this study may represent an example
2022-05-13
The findings in this study may represent an example of a more general phenomenon, namely that the exquisite specificity of the G protein-coupled receptors that mediate the physiological actions of the SLIGKV-NH2 sale family hormones in mammals may have arisen relatively late in evolution. In non-mam
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