Radiative Neutrino Mass with Z3Z_3 Dark matter: From Relic Density to LHC Signatures

In this work we give a comprehensive analysis on the phenomenology of a specific $\mathbb{Z}_3$ dark matter (DM) model in which neutrino mass is induced at two loops by interactions with a DM particle that can be a complex scalar or a Dirac fermion. Both the DM properties in relic density and direct detection and the LHC signatures are examined in great detail, and indirect detection for gamma-ray excess from the Galactic Center is also discussed briefly. On the DM side, both semi-annihilation and co-annihilation processes play a crucial role in alleviating the tension of parameter space between relic density and direct detection. On the collider side, new decay channels resulting from $\mathbb{Z}_3$ particles lead to distinct signals at LHC. Currently the trilepton signal is expected to give the most stringent bound for both scalar and fermion DM candidates, and the signatures of fermion DM are very similar to those of electroweakinos in simplified supersymmetric models.Comment: 40 pages, 24 figure

Quality test of clamping connection of transmission lines across tensile line

This paper develops a new technology for the quality inspection of the transmission line that is important across the tensile clamp. The new technology mainly based on the ultrasonic pulse echo thickness measurement mechanism tests the thickness of the aluminum sleeve after crimping the tensile clamp to reflect the relative position of the aluminum sleeve and the steel anchor after the crimping, thereby judging whether there is a crimping positioning defect. At the same time, it is supplemented by steel anchor model comparison, crimping position length comparison, and crimping to margin detection to determine whether the transmission line crimping quality is qualified

RRM1 single nucleotide polymorphism -37C→A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy

<p>Abstract</p> <p>Background</p> <p>The ribonucleotide reductase M1 (RRM1) gene encodes the regulatory subunit of ribonucleotide reductase, the molecular target of gemcitabine. The overexpression of RRM1 mRNA in tumor tissues is reported to be associated with gemcitabine resistance. Thus, single nucleotide polymorphisms (SNPs) of the RRM1 gene are potential biomarkers of the response to gemcitabine chemotherapy. We investigated whether RRM1 expression in peripheral blood mononuclear cells (PBMCs) or SNPs were associated with clinical outcome after gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC) patients.</p> <p>Methods</p> <p>PBMC samples were obtained from 62 stage IIIB and IV patients treated with gemcitabine-based chemotherapy. RRM1 mRNA expression levels were assessed by real-time PCR. Three RRM1 SNPs, -37C→A, 2455A→G and 2464G→A, were assessed by direct sequencing.</p> <p>Results</p> <p>RRM1 expression was detectable in 57 PBMC samples, and SNPs were sequenced in 56 samples. The overall response rate to gemcitabine was 18%; there was no significant association between RRM1 mRNA expression and response rate (<it>P </it>= 0.560). The median progression-free survival (PFS) was 23.3 weeks in the lower expression group and 26.9 weeks in the higher expression group (<it>P </it>= 0.659). For the -37C→A polymorphism, the median PFS was 30.7 weeks in the C(-)37A group, 24.7 weeks in the A(-)37A group, and 23.3 weeks in the C(-)37C group (<it>P </it>= 0.043). No significant difference in PFS was observed for the SNP 2455A→G or 2464G→A.</p> <p>Conclusions</p> <p>The RRM1 polymorphism -37C→A correlated with PFS in NSCLC patients treated with gemcitabine-based chemotherapy. No significant correlation was found between PBMC RRM1 mRNA expression and the efficacy of gemcitabine.</p

Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression

<p>Abstract</p> <p>Background</p> <p>The anaplastic lymphoma kinase (<it>ALK</it>) gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of <it>ALK </it>include <it>NPM</it>, <it>EML4</it>, <it>TPM3</it>, <it>ATIC</it>, <it>TFG</it>, <it>CARS</it>, and <it>CLTC</it>. Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer.</p> <p>Results</p> <p>RACE-coupled PCR sequencing was used to assess <it>ALK </it>fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC) patients. Within this cohort, the <it>EML4</it>-<it>ALK </it>fusion gene was identified in 12 tumors (11.6%). Further analysis revealed that <it>EML4</it>-<it>ALK </it>was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking <it>EGFR </it>and <it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion was associated with non-smokers (<it>P </it>= 0.03), younger age of onset (<it>P </it>= 0.03), and adenocarcinomas without <it>EGFR</it>/<it>KRAS </it>mutations (<it>P </it>= 0.04). A trend towards improved survival was observed for patients with the <it>EML4</it>-<it>ALK </it>fusion, although it was not statistically significant (<it>P </it>= 0.20). Concurrent deletion in <it>EGFR </it>exon 19 and fusion of <it>EML4</it>-<it>ALK </it>was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the <it>EML</it>-<it>ALK </it>fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; <it>P </it>= 0.0018). However, expression of EML4 did not differ between the groups.</p> <p>Conclusions</p> <p>The <it>EML4</it>-<it>ALK </it>fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking <it>EGFR</it>/<it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of <it>EML4</it>-<it>ALK</it>-positive patients.</p

A Novel Inhibitor of Homodimerization Targeting MyD88 Ameliorates Renal Interstitial Fibrosis by Counteracting TGF-β1-Induced EMT in Vivo and in Vitro

Background/Aims: The TLR/MyD88/NF-κB signaling pathway has been successfully used to treat renal interstitial fibrosis (RIF). However, the exact therapeutic mechanism is still unknown. Here, we assessed the therapeutic efficacy of TJ-M2010-2, a small molecular compound that inhibits MyD88 homodimerization, in RIF induced by ischemia reperfusion injury (IRI). Methods: In vivo, RIF was induced in mice by IRI, and the mice were prophylactically treated with TJ-M2010-2. In vitro, HK-2 cells were incubated with TGF-β1 to induce EMT, and the cells were pretreated with TJ-M2010-2. Results: We found that, compared with the IRI group, the TJ-M2010-2 group showed marked attenuation of RIF and renal function injury; decreased expression of TGF-β1, α-SMA, vimentin, MMP2 and MMP9; and increased E-cadherin expression. Furthermore, TGF-β1-induced EMT was blocked by TJ-M2010-2 in HK-2 cells, as evidenced by blocked morphologic transformation, restored E-cadherin expression and inhibited α-SMA expression. In addition, compared to the TGF-β1 group, the TJ-M2010-2 group showed profound inhibition of the expression of TRAF6, p65 and Snail and upregulation of the expression of IκBα. Conclusion: This MyD88 inhibitor may be a potential therapeutic agent to ameliorate RIF