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1.
Behav Res Methods ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471826

RESUMO

Probability density approximation (PDA) is a nonparametric method of calculating probability densities. When integrated into Bayesian estimation, it allows researchers to fit psychological processes for which analytic probability functions are unavailable, significantly expanding the scope of theories that can be quantitatively tested. PDA is, however, computationally intensive, requiring large numbers of Monte Carlo simulations in order to attain good precision. We introduce Parallel PDA (pPDA), a highly efficient implementation of this method utilizing the Armadillo C++ and CUDA C libraries to conduct millions of model simulations simultaneously in graphics processing units (GPUs). This approach provides a practical solution for rapidly approximating probability densities with high precision. In addition to demonstrating this method, we fit a piecewise linear ballistic accumulator model (Holmes, Trueblood, & Heathcote, 2016) to empirical data. Finally, we conducted simulation studies to investigate various issues associated with PDA and provide guidelines for pPDA applications to other complex cognitive models.

2.
Front Immunol ; 10: 1951, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475012

RESUMO

Chinese herbal medicines used in combination have long-term been shown to be mild remedies with "integrated effects." However, our study provides the first demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, featuring acute renal function impairment, heavy proteinuria, high serum levels of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, and the mice were sacrificed on week 3 and week 5 after the induction of disease. To identify the potential mechanism of action for the pure compound, levels of NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), podocytes and macrophages, and antigen-specific T cell activation in BMDCs were determined in addition to mechanistic experiments in vivo. Treatment with M1 dramatically improved renal function, albuminuria and renal lesions and reduced serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 treatment involved the following cellular and molecular mechanistic events: [1] inhibition of NLRP3 inflammasome associated with autophagy induction, [2] modulation of T help cell activation, and [3] induction of regulatory T cell differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome activation and differentially regulating T cell functions, and the results support M1 as a new therapeutic candidate for LN patients with a status of abrupt transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) nephritis.

3.
Brain Behav Immun ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31479730

RESUMO

Chronic pain and depression are often comorbid exhibiting common clinical presentations and biological connections related to central nervous system sensitization. Epigenetic regulation of gene expression in the brain plays a crucial role in response to long-lasting stress and chronic pain, and microRNA imbalance in the prefrontal cortex (PFC) might be involved in central sensitization. Male Sprague Dawley rats were subjected to unpredictable chronic mild stress (UCMS) and spared nerve injury (SNI) to initiate depressive-like behavior and chronic pain behavior, respectively. The next-generation sequencing technique was employed to analyze PFC microRNAs in both the UCMS and SNI models. Rats exposed to either UCMS or SNI exhibited both depressive-like and chronic pain behaviors. Five specific microRNAs (miR-10a-5p, miR-182, miR-200a-3p, miR-200b-3p, and miR-429) were simultaneously down-regulated in the depressive-like and chronic pain models after 4 weeks of short-term stress. Gene ontology revealed that the 4-week period of stress enhanced neurogenesis. Only the miR-200a-3p level was continuously elevated under prolonged stress, suggesting roles of reduced neurogenesis, inflammatory activation, disturbed circadian rhythm, lipid metabolism, and insulin secretion in the co-existence of pain and depression. Thus we conclude that miR-200a-3p might be a specific biomarker of central sensitization in chronic pain and depression.

4.
Int J Mol Sci ; 20(17)2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480728

RESUMO

Ceramide is a sphingolipid which regulates a variety of signaling pathways in eukaryotic cells. Exogenous ceramide has been shown to induce cellular apoptosis. In this study, we observed that exogenous ceramide induced two distinct morphologies of cell fate following C2-ceramide treatment between the two breast cancer cell lines MCF-7 (wild type p53) and MDA-MB-231 (mutant p53) cells. The growth assessment showed that C2-ceramide caused significant growth inhibition and apoptosis in MDA-MB-231 cells through down-regulating the expression of mutant p53 whereas up-regulating the expression of pro-apoptotic Bad, and the proteolytic activation of caspase-3. However, senescence-associated (SA)-ß-galactosidase (ß-gal) was regulated in MCF-7 cells after C2-ceramide treatment. The results of proliferation and apoptosis assays showed that MCF-7 cells were more resistant to C2-ceramide treatment compared to MDA-MB-231 cells. Furthermore, C2-ceramide treatment induced a time-responsive increase in Rb protein, a key regulator of senescence accompanied with the upregulation of both mRNA level and protein level of SA-genes PAI-1 and TGaseII in MCF-7 but not in MDA-MB-231 cells, suggesting that some cancer cells escape apoptosis through modulating senescence-like phenotype. The results of our present study depicted the mechanism of C2-ceramide-resistant breast cancer cells, which might benefit the strategic development of ceramide-based chemotherapeutics against cancer in the future.

5.
J Chromatogr A ; : 460510, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31515077

RESUMO

In this study, a novel phenyl-boronic acid polymeric monolith (PBAPM) in polyether ether ketone (PEEK) tube was fabricated. The inner wall of PEEK tube was modified with mussel inspired polydopamine layer to firmly bond PBAPM, so as to avoid the outflow of PBAPM from PEEK tube and improve the service life and application scope of PBAPM. The PBAPM was synthesized by initiator-free ring-opening polymerization based on our previous work. The boric acid groups provided B-N coordination sites, as well as the hydrophobic amino and epoxy monomers provided hydrophobic interaction sites. Due to the synergistic effect of hydrophobic interaction and B-N coordination, the PBAPM exhibited excellent binding amounts for nitrogen-containing sulfonamides (SAs). In addition, the PBAPM possessed excellent stability, rigidity and permeability. Therefore, the PBAPM was used as solid phase microextraction (SPME) material for enrichment and separation of SAs from aqueous samples. The PBAPM SPME was optimized in detail, and combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for simultaneous determination of 10 kinds of SAs from tap, lake and river water. Using only 1 mL of water samples, limit of quantitation of SAs could reach 0.54-4.5 ng L-1. Recoveries of standard spiked SAs from water samples were between 82.0% and 105.4%, with intra-day and inter-day relative standard deviation ranging from 3.3% to 5.6% and 4.2% to 8.1%, respectively. The PBAPM SPME combined with UPLC-MS/MS method shown better or similar recoveries, and used fewer samples than previous methods. These results demonstrated that the PBAPM could selectively separate and enrich ultra-trace nitrogen-containing SAs from aqueous samples.

6.
J Zhejiang Univ Sci B ; 20(10): 861-864, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489805

RESUMO

Rectal neuroendocrine neoplasms (NENs) are low-grade malignancies, which are slow-growing and usually become symptomatic late in the course of the disease (Basuroy et al., 2016). In recent years, rectal NENs are increasingly frequently detected, with the widespread availability and accessibility of endoscopy and cross-sectional imaging modalities (Kos-Kudla et al., 2017). Multiple studies have shown that endoscopic ultrasound (EUS) is an advanced endoscopic technique and is currently used in the diagnosis and preoperative assessment of NENs (Kim, 2012; Liu et al., 2013; Zhang et al., 2017). However, EUS imaging of rectal NEN and differential diagnosis with other submucosal tumors (SMTs) has not been adequately reported. In this study, we reviewed and summarized the EUS imaging and pathological features of rectal NENs of 38 cases to improve preoperative diagnosis rate and reduce unreasonable treatment.

7.
Nano Lett ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31502461

RESUMO

Nanosized oncolytic viral light particles (L-particles), separated from progeny virions, are composed of envelopes and several tegument proteins of viruses, free of nucleocapsids. The noninfectious L-particles experience the same internalization process as mature oncolytic virions, which exhibits great potential to act as targeted therapeutic platforms. However, the clinical applications of L-particle-based theranostic platforms are rare due to the lack of effective methods to transform L-particles into nanovectors. Herein, a convenient and mild strategy has been developed to transform L-particles into near-infrared (NIR) fluorescence Ag2Se quantum dot (QD)-labeled active tumor-targeting nanovectors for real-time in situ imaging and drug delivery. Utilizing the electroporation technique, L-particles can be labeled with ultrasmall water-dispersible NIR fluorescence Ag2Se QDs with a labeling efficiency of ca. 85% and loaded with antitumor drug with a loading efficiency of ca. 87%. Meanwhile, by harnessing the infection mechanism of viruses, viral L-particles are able to recognize and enter tumor cells without further modification. In sum, a trackable and actively tumor-targeted theranostics nanovector can be obtained efficiently and simultaneously. Such multifunctional nanovectors transformed from viral L-particles have exhibited excellent properties of active tumor-targeting, in vivo tumor imaging, and antitumor efficacy, which opens a new window for the development of natural therapeutic nanoplatforms.

8.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510092

RESUMO

There is accumulating evidence supporting electroacupuncture's (EA) therapeutic effects. In mice, local EA reliably attenuates inflammatory pain and increases the transient receptor potential cation channel, subfamily V, member 1 (TRPV1). However, the effect of distal acupoint EA on pain control has rarely been studied. We used a mouse model to investigate the analgesic effect of distal EA by measuring TRPV1 expression in the brain. Complete Freund's adjuvant (CFA) was injected into mice's hind paws to induce inflammatory pain. The EA-treated group received EA at the LI4 acupoint on the bilateral forefeet on the second and the third days, whereas the control group underwent sham manipulation. Mechanical and thermal pain behavior tests showed that the EA-treated group experienced inflammatory pain alleviation immediately after EA, which did not occur in the sham group. Additionally, following CFA injection, the expression of TRPV1-associated molecules such as phosphorylated protein kinase A (pPKA), extracelluar signal-regulated kinase (pERK), and cAMP-response-element-binding protein (pCREB) increased in the prefrontal cortex (PFC) and the hypothalamus but decreased in the periaqueductal gray (PAG) area. These changes were significantly attenuated by EA but not sham EA. Our results show an analgesic effect of distal EA, which is based on the traditional Chinese medicine theory. The mechanism underlying this analgesic effect involves TRPV1 in the PFC, the hypothalamus, and the PAG. These novel findings are relevant for the evaluation and the treatment of clinical inflammatory pain syndrome.

9.
Opt Express ; 27(15): 20785-20786, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510167

RESUMO

The editors introduce the feature issue on liquid crystal beyond displays.

10.
Opt Express ; 27(15): 21163-21172, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510198

RESUMO

An optical-see-through augmented reality (AR) system assists our daily work by augmenting our sense with computer-generated information. Two of optical challenges of AR are image registration and vision correction due to fixed optical properties of the optical elements of AR systems. In this paper, we demonstrated an AR system with optical zoom function as well as a function of image registration via two LC lenses in order to help people see better by magnifying the virtual image and adjusting the location of virtual image. The operating principles are introduced, and experiments are performed. The concept demonstrated in this paper could be further extended to other electro-optical devices as long as the devices exhibit the capability of phase modulations.

11.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 343-349, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512823

RESUMO

Periodontal tissue, especially the alveolar bone, are closely associated with the progress and efficacy of orthodontic treatment. Prior to and during orthodontic treatment, dentists should fully evaluate the status of periodontal hard tissues to prevent clinical problems. This article aims to discuss bone issues associated with orthodontic treatment, including gingival papilla absence, alveolar bone insufficiency, excessive cortical resistance, and altered passive eruption, etc. The mechanism and prevention methods of these problems are also described.

12.
Anal Chem ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31475521

RESUMO

Multifunctional probes integrating accurate multidiagnosis and efficient therapy hold great prospects in biomedical research. However, the sophisticated construction and difficulties in matching the ratios of doses and laser triggers of probes for each modal imaging and therapy still hinder the extensive practice of multifunctional probes in biomedicine. We herein rationally designed an organic dye SY1080 with intrinsic multifunction by introducing both 3,4-ethylenedioxy thiophene (EDOT) and the selenium containing acceptor unit into the backbone to balance the fluorescent brightness and emission wavelength. Under single dose and 808 nm laser irradiation conditions, SY1080 not only carried out NIR-II fluorescence/photoacoustic imaging of real-time and noninvasive tumor delineation with excellent contrast, but also effectively ablated tumors with laser irradiation to perform photothermal therapy under the guidance of dual-modal imaging. These exciting results highlight SY1080 as a multifunctional and universal phototheranostic platform for potential applications.

13.
Appl Opt ; 58(18): 5050-5056, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503826

RESUMO

The phase modulation and demodulation technique is widely used in resonant optical gyroscopes to accurately detect resonance frequencies, which directly affect gyro sensitivity. In order to overcome the influences of the system phase fluctuations, an in-phase and quadrature (IQ) demodulation technique is introduced for a resonant micro-optic gyroscope (RMOG). The phase fluctuations in the RMOG are measured, and their influence on the demodulation slope at the resonance point is compared between the traditional sinusoidal demodulation and the IQ demodulation both theoretically and experimentally. It can be concluded that the output of the proposed IQ demodulation is not affected by any phase fluctuations. The demodulation slope is always at its maximum value, thus improving the signal-to-noise ratio of the detection system. By using the IQ demodulation technique, a random walk coefficient of 0.5°/√h is carried out. A long-term bias stability of 9°/h is successfully observed, which is improved by a factor of 1.6 compared with that obtained using the traditional phase-sensitive sinusoidal demodulation technique.

14.
Cell Biol Int ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508857

RESUMO

RASSF4, a member of the classical RASSF family of scaffold proteins, is associated with alveolar rhabdomyosarcoma, an aggressive pediatric cancer of muscle histogenesis. However, the role of RASSF4 in normal myogenesis is unknown. We demonstrate here that RASSF4 is necessary for early in vitro myogenesis. Using primary human myoblasts, we show that RASSF4 expression is dramatically increased during in vitro myogenic differentiation, and conversely that RASSF4-deficient myoblasts cannot differentiate, potentially because of a lack of upregulation of myogenin. In microscopy studies, we show that RASSF4 protein co-localizes with proteins of the myogenic microtubule organizing center (MTOC) both before and after myogenic differentiation. RASSF4-deficient cells subject to differentiation conditions demonstrate a lack of shape change, suggesting that RASSF4 plays a role in promoting microtubule reorganization and myoblast elongation. In biochemical studies of myotubes, RASSF4 associates with MST1, suggesting that RASSF4 signals to MST1 in the myogenic differentiation process. Expression of MST1 in myoblasts partially reversed the effect of RASSF4 knockdown on differentiation, suggesting that RASSF4 and MST1 coordinately support myogenic differentiation. These data show that RASSF4 is critical for the early steps of myogenic differentiation. This article is protected by copyright. All rights reserved.

15.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477838

RESUMO

Tumor invasion and metastasis are the major causes of treatment failure and mortality in lung cancer patients. In this study, we identified a group of genes with differential expression in in situ and invasive lung adenocarcinoma tissues by expression profiling; among these genes we further characterized the association of the upregulation of PRNP, the gene encoding cellular Prion protein (PrPc), with lung adenocarcinoma invasiveness. Immunohistochemistry on clinical specimens showed an association of PrPc expression with invasive but not in situ lung adenocarcinoma. Consistently, the expression of PrPc was higher in the highly invasive than in the lowly invasive lung adenocarcinoma cell lines. Knockdown of PrPc expression in cultured lung adenocarcinoma cells decreased their lamellipodium formation, in vitro migration and invasion, and in vivo experimental lung metastasis. Phosphorylation of JNKs was found to correlate with PrPc expression and the inhibition of JNKs suppressed the PrPc-induced up-regulation of lamellipodium formation, cell migration, and invasion. Moreover, we identified the nuclear factor, interleukin 3 regulated (NFIL3) protein as a transcriptional activator of the PRNP promoter. Accordingly, NFIL3 promoted lung cancer cell migration and invasion in a PrPc-dependent manner. High NFIL3 expression in clinical specimens of lung adenocarcinoma was also associated with tumor invasiveness. Overall, our observations suggest that the NFIL3/PrPc axis, through regulating lamellipodium formation and cell mobility via JNK signaling, plays a critical role in lung cancer invasiveness and metastasis.

16.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477841

RESUMO

Drug resistance is a major problem limiting the efficacy of chemotherapy in cancer treatment, and the hypoxia-induced stabilization of HIF-1α plays a role in this process. HIF-1α overexpression has been observed in a variety of human cancers, including colorectal cancer (CRC). Therefore, targeting HIF-1α is a promising strategy for overcoming chemoresistance to enhance the efficacy of chemotherapies in CRC. Here, we show that DNMT inhibitors can induce HIF-1α degradation to overcome oxaliplatin resistance and enhance anti-CRC therapy. We found that a low-toxicity DNMT inhibitor, zebularine, could downregulate HIF-1α expression and overcome hypoxia-induced oxaliplatin resistance in HCT116 cells and showed efficacy in HCT116 xenograft models and AOM/DSS-induced CRC mouse models. Zebularine could induce the degradation of HIF-1α protein through hydroxylation. LC-MS analysis showed a decrease in succinate in various CRC cells under hypoxia and in colon tissues of AOM/DSS-induced CRC mice. The decrease was reversed by zebularine. Tumor angiogenesis was also reduced by zebularine. Furthermore, zebularine potentiated the anticancer effect of oxaliplatin in AOM/DSS-induced CRC models. This finding provides a new strategy in which an increase in HIF-1α hydroxylation could overcome oxaliplatin resistance to enhance anti-CRC therapy.

17.
Acupunct Med ; : acupmed2017011469, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31517506

RESUMO

BACKGROUND: Inflammatory pain occurs when local tissue injury activates macrophages and neutrophils, hence increasing pro-inflammatory cytokine and chemokine levels. Toll-like receptor 2 (TLR2) antagonism reportedly suppresses neuropathic and inflammatory pain. AIMS: In the present study, we investigated the effect of electroacupuncture (EA) on TLR2 and related signalling molecules in a complete Freund's adjuvant (CFA)-induced mouse model of inflammatory pain to determine whether EA can attenuate inflammatory pain via the TLR2 signalling pathway. METHODS: EA significantly reduced mechanical and thermal hyperalgesia in the animal model. A similar effect was produced by TLR2 antagonism induced by CU-CPT22 injection. RESULTS: TLR2 expression in the dorsal root ganglia, spinal cord and thalamus increased following induction of inflammation. Expression levels of downstream molecules such as pPI3K, pAkt and pmTOR also increased, as did those of MAPK subfamily members such as pERK, pp38 and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were also involved. CONCLUSION: Increased expression of the above molecules was attenuated by both EA and TLR2 antagonism. Our results show that EA attenuates inflammatory pain via TLR2 signalling.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31446199

RESUMO

Axicabtagene ciloleucel (YESCARTA®, Kite Pharma, a Gilead Company) and tisagenlecleucel (KYMRIAH®, Novartis Pharmaceuticals Corp.) are two CD19-directed chimeric antigen receptor T cell (CD19 CAR T) products that are currently approved by the U.S. Food and Drug Administration, the European Medicines Agency, Health Canada, Ministry of Health, Labor and Welfare (Japan) and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/ refractory aggressive B cell non-Hodgkin lymphoma (NHL). While this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate utilization of this novel therapy, as well as short- and long-term toxicities. To address these issues, representatives of American Society of Transplantation and Cellular Therapy (ASTCT) convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts and members of International Society of Cell and Gene Therapy (ISCT), American Society of Hematology (ASH), Foundation for the Accreditation of Cellular Therapy (FACT) and European Society for Blood and Marrow Transplantation (EBMT). The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the utilization of CD19 CAR T for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.

19.
Am J Reprod Immunol ; 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31446642

RESUMO

PROBLEM: Preeclampsia (PE) is a unique gestational disorder leading to maternal and neonatal morbidity and mortality. AnnexinA7 (ANXA7) is a calcium-dependent phospholipid binding protein that promotes membrane fusion during exocytosis. However, the function of ANXA7 in placental trophoblast is poorly understood. The present study aimed to investigate a possible association between ANXA7 and human trophoblast apoptosis. METHODS: We collected human placental tissues from patients with PE and normal pregnant women to elucidate the expression level of ANXA7. The ANXA7-knockdown and ANXA7-overexpressing HTR8/SVneo cells were utilized for studying the function of ANXA7 in trophoblast. The proliferation and apoptosis levels of trophoblast were examined with western blot assay, flow cytometry, Cell Counting Kit-8 assay and immunohistochemistry. RESULTS: ANXA7 expression was significantly lower in placentas from patients with PE patients compared with that in from normal pregnant controls. Knockdown of ANXA7 induced cell apoptosis and inhibited cell proliferation in HTR-8 via by downregulating BCL2 protein levels. Overexpression of ANXA7 reduced apoptosis and promoted HTR8 proliferation. Further analyses showed that ANXA7 knockdown inhibited the activation of the JAK1/STAT3 pathway in HTR-8 cells. CONCLUSIONS: Our findings revealed a new regulatory pathway of ANXA7/JAK1/STAT3 in trophoblast apoptosis in preeclampsia, suggesting that ANXA7 is a potential therapeutic target for preeclampsia.

20.
Cell Rep ; 28(6): 1538-1550.e7, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390567

RESUMO

Ras GTPases are mutated at codons 12, 13, and 61, with different frequencies in KRas, HRas, and NRas and in a cancer-specific manner. The G13D mutant appears in 25% of KRas-driven colorectal cancers, while observed only rarely in HRas or NRas. Structures of Ras G13D in the three isoforms show an open active site, with adjustments to the D13 backbone torsion angles and with disconnected switch regions. KRas G13D has unique features that destabilize the nucleotide-binding pocket. In KRas G13D bound to GDP, A59 is placed in the Mg2+ binding site, as in the HRas-SOS complex. Structure and biochemistry are consistent with an intermediate level of KRas G13D bound to GTP, relative to wild-type and KRas G12D, observed in genetically engineered mouse models. The results explain in part the elevated frequency of the G13D mutant in KRas over the other isoforms of Ras.

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