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Finally we assessed the utility of monitoring cfDNA
2020-08-10

Finally, we assessed the utility of monitoring cfDNA in terms of predicting disease progression earlier than radiological progression. These patients may have a chance to receive subsequent chemotherapy before worsening symptoms. Although the number of the patients who experienced progression was re
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br Introduction Biocatalysis can be used to synthesize
2020-08-08

Introduction Biocatalysis can be used to synthesize chiral building blocks, such as monomers for polymer materials, and precursors for pharmaceuticals [[1], [2], [3], [4]]. Enzymes are very suitable for catalyzing reactions with high enantioselectivity to obtain chiral products. For instance, alc
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Almost of drugs in the market
2020-08-08

Almost 75% of drugs in the market undergo deactivation though oxidation, reduction or hydrolysis by cytochrome P450 (CYP) enzymes, and then, either directly or by facilitated excretion from the body (Guengerich, 2008). The CYP3A subfamily is of particular interest because of its broad substrate spec
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One possibility to differentiate between
2020-08-08

One possibility to differentiate between the two failure modes, and also to identify the corresponding characteristics of the resulting fracture surface, is a series of FNCT measurements with varying nominal (initial) stress. The dependence of the observed time to failure tf on the actual stress cha
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The DDRs can interact with multiple proteins
2020-08-08

The DDRs can interact with multiple proteins and also modulate signaling pathways initiated by other matrix receptors, cytokines,growth factors, and transmembrane receptors in a context- and cell-type-dependent manner.3, 4 We therefore evaluated the consequences of DDR2 activation on potential downs
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Clotrimazole belongs to the imidazole group
2020-08-08

Clotrimazole belongs to the imidazole group, often used for treatment of fungal infections. It decreases fungal growth by inhibiting CYP51 conversion of lanosterol to ergosterol, an essential component of fungal cell membranes (Rozman and Waterman, 1998). As CLO acts via the inhibition of the CYP51-
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Coactivator binding induces substantial APC
2020-08-07

Coactivator binding induces substantial APC/C conformational changes that globally shift the platform and catalytic core into proximity of the substrate-binding module and increase the mobility of domains contributing to catalysis 21, 24 (Figures 2 A and 4 B). Most strikingly, repositioning of APC4
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br Common features of TdT
2020-08-07

Common features of TdT, pol μ and pol λ TdT, pol μ and pol λ remain in a closed conformation throughout their catalytic cycle, contrary to pol β [24•, 53, 54•]. One possible explanation for this observation is that they have traded fidelity (which requires open-to-closed transition) for a very ti
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br Combination approaches to increase efficacy of
2020-08-07

Combination approaches to increase efficacy of DHODH inhibitors Results from the multitude of de novo pyrimidine inhibitors in anticancer clinical trials depict a mixed outlook for single agent DHODH inhibition. As previously discussed, brequinar produced minimal objective responses in clinical t
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The question remains however as to
2020-08-06

The question remains, however as to the downstream signaling by Epacs that contributes to persistent sensitization of sensory neurons. Activation of the Ras family of GTPases by Epac1 (RapGEF3) or Epac2 (RapGEF4) (Bos, 2003, de Rooij et al., 1998) is linked to a number of downstream signaling effect
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Historically covalent drugs have had great
2020-08-06

Historically, covalent drugs have had great success (e.g., aspirin and penicillin), and covalent drugs have become a focus in anticancer and antiviral drug discovery (Kalgutkar and Dalvie, 2012, Singh et al., 2011). These compounds contain low reactivity warheads that allow covalent adducts to form
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SUMOylation involves a three step
2020-08-06

SUMOylation involves a three-step enzyme pathway for the attachment of SUMO to its target proteins (Park et al, 2011). The first step is the activation of mature SUMO by a SUMO-specific E1 activating enzyme, which promotes C-terminal binding of SUMO to AMP (SUMO-AMP) in an ATP-dependent reaction. Th
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Because chemokines and chemokine receptors play an important
2020-08-06

Because chemokines and chemokine receptors play an important role in the immune system [26], they have been extensively studied in mammals. For example, Matsuo [27] reported that the CXC-type chemokine/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer. Zou [28] re
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CXC chemokines not only have vital roles in development
2020-08-06

CXC chemokines not only have vital roles in development and homeostasis but also participate in inflammatory responses in humans (Zlotnik and Yoshie, 2000, 2012; Raman et al., 2011). Conversely, the involvement of CXC chemokines in immune responses in fish species has only been sporadically reported
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br Methods Adult male B CRHtklee mice g
2020-08-06

Methods Adult male B6, 129 CRHtklee mice (25–30g at the beginning of the experiments) that were wild-type (CRF1R+/+) and recessive homozygous or knockout (CRF1R−/−) were housed six per cage. Mice were 3–5months old and derived from mating CRF1R+/− breeders (Jackson Laboratory, California). Wild-t
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