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Research provides ample evidence for an association between
2020-08-03
Research provides ample evidence for an association between changes in opioid signalling and changes in social behaviours in animals. Only a small number of studies attempted to determine whether such associations occur in people as well. Troisi et al. (2011) investigated whether a common polymorphi
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A key inciting event in
2020-08-03
A key inciting event in atherosclerosis is the deposition of circulating low-density lipoprotein (LDL) in the subendothelial space of major arteries. In the subendothelium, native LDL is no longer protected by circulating antioxidants and is oxidatively modified to oxidized LDL (OxLDL) [5]. OxLDL is
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Like other Ub Ubl modifiers
2020-08-03
Like other Ub/Ubl modifiers, the process of protein UFMylation is controlled by an E1–E2–E3 enzymatic cascade (). First, the UFM1 activating E1 enzyme (UBA5) catalyzes the ATP-dependent adenylation of the UFM1 C-terminal carboxylate., The subsequent intermolecular nucleophilic attack of the UFM1-ade
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Up to the date of writing
2020-08-03
Up to the date of writing, there are no published clinical studies that would have compared treatment outcome of GBM patients after radiotherapy depending on tumor PARP-1 and DNA-PK expression levels. Therefore, the data of the present study cannot be compared with similar studies. In spite of that,
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Monomethyl derivative would be expected to
2020-08-03
Monomethyl derivative 14 would be expected to dramatically reduce the potential for metabolic activation of the substituted carbon center, as well as any metabolic activation leading to a much less reactive keto-metabolite. In parallel to this design effort, a more detailed evaluation of the metabol
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The present work lays the groundwork for reactor
2020-08-03
The present work lays the groundwork for reactor engineering, required for proper scaling of synthesis. An enzyme’s kinetic mechanism (the order and manner of substrate binding and product release) determines its kinetic rate law. The rate law defines the turnover rate as a function of substrate con
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Patients were then followed with regular audiologic assessme
2020-08-01
Patients were then followed with regular audiologic assessments, with an average of 5.8 assessments being performed on each study participant. The primary endpoint was the change between baseline and follow-up in the hearing scores corresponding to the best ear at each audiologic follow-up time poin
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br Cytochrome P monooxygenases Cytochrome P monooxygenases P
2020-07-31
Cytochrome P450 monooxygenases Cytochrome P450 monooxygenases (P450s) belong to one of Nature’s most versatile group of enzymes for C–H functionalization and are able to perform challenging regioselective and stereoselective activations of remote, unactivated C(sp3)–H bonds, for which there are o
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LPA is known to regulate
2020-07-31
LPA is known to regulate the peroxisome proliferator-activated receptor γ and the reorganization of BI 6015 synthesis cytoskeleton [58]. However, the physiological functions of LPA in cells are still poorly understood. The simultaneous production of PA with/without 1-LPA or 2-LPA may be important t
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Fmoc-D-Lys(Boc)-OH The fast delivery of novel chemical entit
2020-07-31
The fast delivery of novel chemical entities (NCEs) alone does not guarantee success in any drug discovery project. One factor that should also be taken into account is that optimization from hit to lead and then to drug is a very time consuming and expensive process with high attrition rate (Bleich
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In all available crystal structures
2020-07-31
In all available crystal structures of TS-DHFR, a non-active site pocket which may accommodate small molecules is formed just above the crossover helix and adjacent to the DHFR domain of the bifunctional protein (B). Residues from both the crossover helix and Helix B of the DHFR catalytic domain for
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Upregulation of RTKs is a common mechanism underlying TKI
2020-07-30
Upregulation of RTKs is a common mechanism underlying TKI resistance (Camidge et al., 2014, Minari et al., 2016). A single tumor with heterogeneous resistance mechanisms may upregulate multiple RTKs and cause failure of the combination therapy of TKI and specific RTK inhibitors (Figure 6G). Here, we
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The present work together with our
2020-07-30
The present work, together with our previous study, offers a means of conferring collagen-binding integrin-, VWF- and DDR-reactivity upon an inert substrate. GPRGQOGVNleGFO is known to bind not only VWF and DDR2, but also DDR1 and SPARC (Secreted Protein Acidic and Rich in Cysteine) [20,52]. We ther
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As temperatures increase rates of spontaneous deamination al
2020-07-30
As temperatures increase, rates of spontaneous deamination also increase such that hyperthermophilic organisms must have efficient mechanisms for dealing with this potential hazard.8., 9. The hyperthermophile Methanococcus jannaschii has both a dCTP deaminase (encoded by the gene at locus MJ0430) an
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The term myeloproliferative disorders was first proposed by
2020-07-30
The term “myeloproliferative disorders” was first proposed by William Dameshek in 1951. With the discovery of the Philadelphia chromosome, myeloproliferative disorders were classified into two groups: BCR-ABL positive chronic myeloid leukemia (CML) and BCR-ABL negative chronic myeloproliferative dis
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