Fast simultaneous detection of K-RAS mutations in colorectal cancer

<p>Abstract</p> <p>Background</p> <p><it>RAS </it>genes acquire the most common somatic gain-of-function mutations in human cancer, and almost all of these mutations are located at codons 12, 13, 61, and 146.</p> <p>Methods</p> <p>We present a method for detecting these <it>K-RAS </it>hotspot mutations in 228 cases of colorectal cancer. The protocol is based on the multiplex amplification of exons 2, 3 and 4 in a single tube, followed by primer extension of the PCR products using various sizes of primers to detect base changes at codons 12, 13, 61 and 146. We compared the clinicopathological data of colorectal cancer patients with the <it>K-RAS </it>mutation status.</p> <p>Results</p> <p><it>K-RAS </it>mutation occurred in 36% (83/228) of our colorectal cancer cases. Univariate analysis revealed a significant association between <it>K-RAS </it>mutation at codon 12 of exon 2 and poor 5-year survival (p = 0.023) and lymph node involvement (p = 0.048). Also, <it>K-RAS </it>mutation at codon 13 of exon 2 correlates with the size of the tumor (p = 0.03). Multivariate analysis adjusted for tumor size, histologic grade, and lymph node metastasis also indicated <it>K-RAS </it>mutations at codon 12 and 13 of exon 2 correlate significantly with overall survival (p = 0.002 and 0.025). No association was observed between codon 61 and 146 and clinicopathological features.</p> <p>Conclusion</p> <p>We demonstrated a simple and fast way to identify <it>K-RAS </it>mutation.</p

Spectrum of the Vortex Bound States of the Dirac and Schrodinger Hamiltonian in the presence of Superconducting Gaps

We investigate the vortex bound states both Schrodinger and Dirac Hamiltonian with the s-wave superconducting pairing gap by solving the mean-field Bogoliubov-de-Gennes equations. The exact vortex bound states spectrum is numerically determined by the integration method, and also accompanied by the quasi-classical analysis. It is found that the bound state energies is proportional to the vortex angular momentum when the chemical potential is large enough. By applying the external magnetic field, the vortex bound state energies of the Dirac Hamiltonian are almost unchanged; whereas the energy shift of the Schrodinger Hamiltonian is proportional to the magnetic field. These qualitative differences may serve as an indirect evidence of the existence of Majorana fermions in which the zero mode exists in the case of the Dirac Hamiltonian only.Comment: 8 pages, 9 figure

Tribological properties of nitrogen implanted and boron implanted steels

Samples of a steel with high chrome content was implanted separately with 75 keV nitrogen ions and with 75 keV boron ions. Implanted doses of each ion species were 2-, 4-, and 8 {times} 10{sup 17}/cm{sup 2}. Retained doses were measured using resonant non-Rutherford Backscattering Spectrometry. Tribological properties were determined using a pin-on-disk test with a 6-mm diameter ruby pin with a velocity of 0.94 m/min. Testing was done at 10% humidity with a load of 377 g. Wear rate and coefficient of friction were determined from these tests. While reduction in the wear rate for nitrogen implanted materials was observed, greater reduction (more than an order of magnitude) was observed for boron implanted materials. In addition, reduction in the coefficient of friction for high-dose boron implanted materials was observed. Nano-indentation revealed a hardened layer near the surface of the material. Results from grazing incidence x-ray diffraction suggest the formation of Fe{sub 2}N and Fe{sub 3}N in the nitrogen implanted materials and Fe{sub 3}B in the boron implanted materials. Results from transmission electron microscopy will be presented

Quantum algebra in the mixed light pseudoscalar meson states

In this paper, we investigate the entanglement degrees of pseudoscalar meson states via quantum algebra Y(su(3)). By making use of transition effect of generators J of Y(su(3)), we construct various transition operators in terms of J of Y(su(3)), and act them on eta-pion-eta mixing meson state. The entanglement degrees of both the initial state and final state are calculated with the help of entropy theory. The diagrams of entanglement degrees are presented. Our result shows that a state with desired entanglement degree can be achieved by acting proper chosen transition operator on an initial state. This sheds new light on the connect among quantum information, particle physics and Yangian algebra.Comment: 9 pages, 3 figure

The fermion dynamical symmetry model for the even--even and even--odd nuclei in the Xe--Ba region

The even--even and even--odd nuclei $^{126}$Xe-$^{132}$Xe and $^{131}$Ba-$^{137}$Ba are shown to have a well-realized $SO_8 \supset SO_6 \supset SO_3$ fermion dynamical symmetry. Their low-lying energy levels can be described by a unified analytical expression with two (three) adjustable parameters for even--odd (even--even) nuclei that is derived from the fermion dynamical symmetry model. Analytical expressions are given for wavefunctions and for $E2$ transition rates that agree well with data. The distinction between the FDSM and IBM $SO_6$ limits is discussed. The experimentally observed suppression of the the energy levels with increasing $SO_5$ quantum number $\tau$ can be explained as a perturbation of the pairing interaction on the $SO_6$ symmetry, which leads to an $SO_5$ Pairing effect for $SO_6$ nuclei.Comment: submitted to Phys. Rev. C, LaTeX, 31 pages, 8 figures with postscript files available on request at [email protected]

The synthesized 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) promoted G2/M arrest through inhibition of CDK1 and induced apoptosis through the mitochondrial-dependent pathway in CT-26 murine colorectal adenocarcinoma cells

In this study, we investigated the effects of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) on cell viability, cell cycle arrest and apoptosis in CT-26 murine colorectal adenocarcinoma cells. For determining cell viability, the MTT assay was used. CHM-1 promoted G2/M arrest by PI staining and flow cytometric analysis. Apoptotic cells were evaluated by DAPI staining. We used CDK1 kinase assay, Western blot analysis and caspase activity assays for examining the CDK1 activity and proteins correlated with apoptosis and cell cycle arrest. The in vivo anti-tumor effects of CHM-1-P were evaluated in BALB/c mice inoculated with CT-26 cells orthotopic model. CHM-1 induced CT-26 cell viability inhibition and morphologic changes in a dose-dependent and time-dependent manner and the approximate IC(50) was 742.36 nM. CHM-1 induced significant G2/M arrest and apoptosis in CT-26 cells. CHM-1 inhibited the CDK1 activity and decreased CDK1, Cyclin A, Cyclin B protein levels. CHM-1 induced apoptosis in CT-26 cells and promoted increasing of cytosolic cytochrome c, AIF, Bax, BAD, cleavage of pro-caspase-9, and -3. The significant reduction of caspase-9 and -3 activity and increasing the viable CT-26 cells after pretreated with caspase-9 and -3 inhibitor indicated that CHM-1-induced apoptosis was mainly mediated a mitochondria-dependent pathway. CHM-1-P improved mice survival rate, and enlargement of the spleen and liver metastasis were significantly reduced in groups treated with either 10 mg/kg and 30 mg/kg of CHM-1-P and 5-FU in comparison to these of CT-26/BALB/c mice. Taken together, CHM-1 acted against colorectal adenocarcinoma cells in vitro via G2/M arrest and apoptosis, and CHM-1-P inhibited tumor growth in vivo

Narrative Exposure Therapy for Posttraumatic Stress Disorder associated with repeated interpersonal trauma in patients with Severe Mental Illness: a mixed methods design

Background: In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the understanding of quantitative outcomes. Discussion: The results of this study will provide more insight into influencing factors for clinical changes in this population

Semileptonic decays of Bs1B_{s1}, Bs2∗B_{s2}^*, Bs0B_{s0} and Bs1′B_{s1}'

Stimulated by recent observations of the excited bottom-strange mesons $B_{s1}$ and $B_{s2}^*$, we calculate the semileptonic decays $B_{s0}, B_{s1}^{\prime}, B_{s1}, B_{s2}^*\to [D_s(1968), D_{s}^*(2112), D_{sJ}(2317), D_{sJ}(2460)]\ell\bar{\nu}$, which is relevant for the exploration of the potential of searching these semileptonic decays in experiment.Comment: 11 pages, 3 figures, 9 tables. More discussion added, some descriptions changed. The version to appear in EPJ

Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters