TIP-1 Translocation onto the Cell Plasma Membrane Is a Molecular Biomarker of Tumor Response to Ionizing Radiation

Tumor response to treatment has been generally assessed with anatomic and functional imaging. Recent development of in vivo molecular and cellular imaging showed promise in time-efficient assessment of the therapeutic efficacy of a prescribed regimen. Currently, the in vivo molecular imaging is limited with shortage of biomarkers and probes with sound biological relevance. We have previously shown in tumor-bearing mice that a hexapeptide (HVGGSSV) demonstrated potentials as a molecular imaging probe to distinguish the tumors responding to ionizing radiation (IR) and/or tyrosine kinase inhibitor treatment from those of non-responding tumors.In this study we have studied biological basis of the HVGGSSV peptide binding within the irradiated tumors by use of tumor-bearing mice and cultured cancer cells. The results indicated that Tax interacting protein 1 (TIP-1, also known as Tax1BP3) is a molecular target that enables the selective binding of the HVGGSSV peptide within irradiated xenograft tumors. Optical imaging and immunohistochemical staining indicated that a TIP-1 specific antibody demonstrated similar biodistribution as the peptide in tumor-bearing mice. The TIP-1 antibody blocked the peptide from binding within irradiated tumors. Studies on both of human and mouse lung cancer cells showed that the intracellular TIP-1 relocated to the plasma membrane surface within the first few hours after exposure to IR and before the onset of treatment associated apoptosis and cell death. TIP-1 relocation onto the cell surface is associated with the reduced proliferation and the enhanced susceptibility to the subsequent IR treatment.This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer

Study on coal seam physical characteristics and influence on stimulation: A case study of coal seams in zhengzhuang block

Coalbed Methane (CBM) is an unconventional form of natural gas which is self-generated and self-stored in coal seams. In order to realize the effective exploitation of CBM in Zhengzhuang block, microstructure, wettability, permeability, rock mechanics and in-situ stress of coal were studied in this research. It is found that high rank anthracite characterized by high vitrinite content and low inorganic mineral content, is abundant in CBM. More than 96% of inorganic minerals are clays dominated by kaolinite and illite. Various types of pores are developed on the coal. The wettability of coal differs from high to low to surface water, active water, and foam fracturing fluid; and contact angles of coal with active water and foam fracturing fluid decrease with the increase of burial depth. Gradients of fracture pressure and closure pressure in No.3 coal seam are higher than that of No.15 coal seam. The elastic modulus of coal is lower than that of sandstone. The construction curve of hydraulic fracturing shows that, when the construction flow rate and sand quantity are similar, the construction pressure of prepad in No.3 coal seam is lower than the pumping pressure of No.15 coal seam, but the propagated pressure is higher than that of No.15 coal seam. The drainage effect of No.3 coal seam with large pore volume, shallow burial depth and obvious fracture pressure is better than that of No.15 coal seam. The comprehensive understanding of coal physical properties and engineering practice in the block provide certain guiding significance to the CBM exploitation in Qinshui Basin

Linker-extended native cyanovirin-N facilitates PEGylation and potently inhibits HIV-1 by targeting the glycan ligand

Cyanovirin-N (CVN) potently inhibits human immunodeficiency virus type 1 (HIV-1) infection, but both cytotoxicity and immunogenicity have hindered the translation of this protein into a viable therapeutic. A molecular docking analysis suggested that up to 12 residues were involved in the interaction of the reverse parallel CVN dimer with the oligosaccharide targets, among which Leu-1 was the most prominent hot spot residue. This finding provided a possible explanation for the lack of anti-HIV-1 activity observed with N-terminal PEGylated CVN. Therefore, linker-CVN (LCVN) was designed as a CVN derivative with a flexible and hydrophilic linker (Gly4Ser)3 at the N-terminus. The N-terminal α-amine of LCVN was PEGylated to create 10 K PEG-aldehyde (ALD)-LCVN. LCVN and 10 K PEG-ALD-LCVN retained the specificity and affinity of CVN for high mannose N-glycans. Moreover, LCVN exhibited significant anti-HIV-1 activity with attenuated cytotoxicity in the HaCaT keratinocyte cell line and MT-4 T lymphocyte cell lines. 10 K PEG-ALD-LCVN also efficiently inactivated HIV-1 with remarkably decreased cytotoxicity and pronounced cell-to-cell fusion inhibitory activity in vitro. The linker-extended CVN and the mono-PEGylated derivative were determined to be promising candidates for the development of an anti-HIV-1 agent. This derivatization approach provided a model for the PEGylation of biologic candidates without introducing point mutations. © 2014 Chen et al

Search for resonances in the mass spectrum of muon pairs produced in association with b quark jets in proton-proton collisions at root 8 and 13 TeV

A search for resonances in the mass range 12-70 GeV produced in association with a b quark jet and a second jet, and decaying to a muon pair, is reported. The analysis is based on data from proton-proton collisions at center-of-mass energies of 8 and 13 TeV, collected with the CMS detector at the LHC and corresponding to integrated luminosities of 19.7 and 35.9 fb(-1), respectively. The search is carried out in two mutually exclusive event categories. Events in the first category are required to have a b quark jet in the central region (|| 2.4) and at least one jet in the forward region (|| > 2.4). Events in the second category are required to have two jets in the central region, at least one of which is identified as a b quark jet, no jets in the forward region, and low missing transverse momentum. An excess of events above the background near a dimuon mass of 28 GeV is observed in the 8 TeV data, corresponding to local significances of 4.2 and 2.9 standard deviations for the first and second event categories, respectively. A similar analysis conducted with the 13 TeV data results in a mild excess over the background in the first event category corresponding to a local significance of 2.0 standard deviations, while the second category results in a 1.4 standard deviation deficit. The fiducial cross section measurements and 95% confidence level upper limits on those for a resonance consistent with the 8 TeV excess are provided at both collision energies

Search for vector-like T and B quark pairs in final states with leptons at s=13 \sqrt{s}=13 TeV

A search is presented for pair production of heavy vector-like T and B quarks in proton-proton collisions at s √ =13 s=13 TeV. The data sample corresponds to an integrated luminosity of 35.9 fb−1, collected with the CMS detector at the CERN LHC in 2016. Pair production of T quarks would result in a wide range of final states, since vector-like T quarks of charge 2e/3 are predicted to decay to bW, tZ, and tH. Likewise, vector-like B quarks are predicted to decay to tW, bZ, and bH. Three channels are considered, corresponding to final states with a single lepton, two leptons with the same sign of the electric charge, or at least three leptons. The results exclude T quarks with masses below 1140–1300 GeV and B quarks with masses below 910–1240 GeV for various branching fraction combinations, extending the reach of previous CMS searches by 200–600 GeV

Search for the pair production of light top squarks in the e(+/-)mu(-/+) final state in proton-proton collisions at root s=13 TeV

A search for the production of a pair of top squarks at the LHC is presented. This search targets a region of parameter space where the kinematics of top squark pair production and top quark pair production are very similar, because of the mass difference between the top squark and the neutralino being close to the top quark mass. The search is performed with 35.9 fb(-1) of proton-proton collisions at a centre-of-mass energy of root s = 13 TeV, collected by the CMS detector in 2016, using events containing one electron-muon pair with opposite charge. The search is based on a precise estimate of the top quark pair background, and the use of the M-T2 variable, which combines the transverse mass of each lepton and the missing transverse momentum. No excess of events is found over the standard model predictions. Exclusion limits are placed at 95% confidence level on the production of top squarks up to masses of 208 GeV for models with a mass difference between the top squark and the lightest neutralino close to that of the top quark.Peer reviewe

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

Search for beyond the standard model Higgs bosons decaying into a b(b)over-bar pair in pp collisions at root s=13 TeV

A search for Higgs bosons that decay into a bottom quark-antiquark pair and are accompanied by at least one additional bottom quark is performed with the CMS detector. The data analyzed were recorded in proton-proton collisions at a centre-of-mass energy of root s = 13TeV at the LHC, corresponding to an integrated luminosity of 35.7 fb(-1). The final state considered in this analysis is particularly sensitive to signatures of a Higgs sector beyond the standard model, as predicted in the generic class of two Higgs doublet models (2HDMs). No signal above the standard model background expectation is observed. Stringent upper limits on the cross section times branching fraction are set for Higgs bosons with masses up to 1300 GeV. The results are interpreted within several MSSM and 2HDM scenarios.Peer reviewe