Circular RNAs as a potential source of neoepitopes in cancer.

Neoepitopes have attracted much attention as targets for immunotherapy against cancer. Therefore, efficient neoepitope screening technology is an essential step in the development of personalized vaccines. Circular RNAs (circRNAs) are generated by back-splicing and have a single-stranded continuous circular structure. So far, various circRNAs have been poorly characterized, though new evidence suggests that a few translated circRNAs may play a role in cancer. In the present study, circRNA was used as a source of neoepitope, a novel strategy as circRNA-derived neoepitopes have never been previously explored. The present study reports CIRC_neo (circRNA-derived neoepitope prediction pipeline), which is a comprehensive and automated bioinformatic pipeline for the prediction of circRNA-derived neoepitopes from RNA sequencing data. The computational prediction from sequencing data requires complex computational workflows to identify circRNAs, derive the resulting peptides, infer the types of human leukocyte antigens (HLA I and HLA II) in patients, and predict the neoepitopes binding to these antigens. The present study proposes a novel source of neoepitopes. The study focused on cancer-specific circRNAs, which have greatly expanded the source pool for neoepitope discovery. The statistical analysis of different features of circRNA-derived neoepitopes revealed that circRNAs could produce long proteins or truncated proteins. Because the peptides were completely foreign to the human body, they could be highly immunogenic. Importantly, circRNA-derived neoepitopes capable of binding to HLA were discovered. In the current study, circRNAs were systematically analyzed, revealing potential targets and novel research clues for cancer diagnosis, treatment, and prospective personalized vaccine research.

Stress Relief and Permeability Enhancement with Hydraulic Fracturing in Overlying Key Strata of Deep and Soft Coal Seams.

The technical problems of high in situ stress, high gas pressure, high gas content, and low coal seam permeability are widespread in deep soft coal seam excavation, which leads to frequent occurrences of dynamic phenomena, such as coal cannons and blowout holes. Based on the high-pressure hydraulic fracturing technology and process, this study puts forward a new technology of gas drainage in deep and soft coal seams by fracturing the overlying key strata to cut off the stress transmission path among coal and rock strata. According to the theories of key layer and masonry beams, the distribution locations of the main and subkey strata are determined, and based on uniaxial compression and Brazilian splitting experiments, the mechanical parameters of key stratum were tested. Combined with the results of numerical simulation and field test, initial pressure and fracturing radius of hydraulic fracturing technology for overlying key strata were determined, the stress relief effect and permeability variation law of coal seam after hydraulic fracturing in the main and subkey strata were analyzed, and then technical schemes for simultaneous fracturing of the key layer were designed. Field application results showed that the stress concentration phenomenon in soft coal seam excavation had been alleviated, and the stress relief effect of coal seam and the permeability were increased obviously. The volume and concentration of gas drainage were increased by 10 and 11%, respectively, the gas amount by 1.22 times; the frequency of dynamic phenomena such as coal cannons decreased by 95%, the gas concentration in return air flow by 20% during mining processes. This paper provided an innovative technical idea and process for gas control in deep and soft coal seam excavation, which could effectively solve the common and difficult problems about frequent occurrences of excessive gas concentration and dynamic phenomena.

Frequency response characteristics and failure model of single-layered thin plate rock mass under dynamic loading.

In underground engineering, disturbance of dynamic load can change layered rock mass stress state and induce accidents. Traditional elastic mechanics can't effectively solve the complex deformation problem. However, Hamiltonian mechanics system can overcome this problem. Dual variables are introduced in symplectic space to solve the deflection equations of single-layered thin plate rock mass. Comparing vibration parameters, it's found the 1st, 5th and 6th order are effective vibration modes. The resonance characteristics of thin plate are obtained with three dynamic loads. It's found the thin plate is most likely to resonate and damage due to the smallest resonance frequency interval and the largest vibration amplitude by impact wave and rectangular wave respectively. Then, the vibration mode of multi-layered rock mass is analyzed through Multiple Reference Impact Testing. The failure of fine sandstone is caused by the resonance of effective vibration modes by hammer excitation. Finally, the failure mechanism of thin plate is obtained by the failure theory and LS-DYNA. It's found the four sides and corners suffer tensile shear failure and shear failure respectively. When tensile failure occurs in central, the main crack and secondary crack propagate along long axis and short axis to form "O-" failure mode.

Radiation dosimetry in digital breast tomosynthesis: report of AAPM Tomosynthesis Subcommittee Task Group 223.

The radiation dose involved in any medical imaging modality that uses ionizing radiation needs to be well understood by the medical physics and clinical community. This is especially true of screening modalities. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Therefore, it is important that the medical physics community have the required information to be able to understand, estimate, and communicate the radiation dose levels involved in breast tomosynthesis imaging. For this purpose, the American Association of Physicists in Medicine Task Group 223 on Dosimetry in Tomosynthesis Imaging has prepared this report that discusses dosimetry in breast imaging in general, and describes a methodology and provides the data necessary to estimate mean breast glandular dose from a tomosynthesis acquisition. In an effort to maximize familiarity with the procedures and data provided in this Report, the methodology to perform the dose estimation in DBT is based as much as possible on that used in mammography dose estimation.

Effect of Cu content on the antibacterial activity of titanium-copper sintered alloys.

The phase constitution and the microstructure Ti-x Cu (x=2, 5, 10 and 25 wt.%) sintered alloys were investigated by XRD and SEM and the antibacterial activity was assessed in order to investigate the effect of the Cu content on the antibacterial activity. The results have shown that Ti2Cu was synthesized as a main secondary phase in all Ti-Cu alloys while Cu-rich phase was formed in the alloys with 5 wt.% or more copper. Antibacterial tests have showed that the Cu content influences the antibacterial rate seriously and only the alloys with 5 wt.% or high Cu have a strong and stable antibacterial rate, which indicates that the Cu content in Ti-Cu alloys must be at least 5 wt.% to obtain strong and stable antibacterial property. The Cu content also influenced the Cu ion release behavior. High Cu ion release concentration and high Cu ion release rate were observed for Ti-Cu alloys with high Cu content. It was concluded that the Cu content affects the Cu existence and the Cu ion release behavior, which in turn influences the antibacterial property. It was thought that the Cu-rich phase should play an important role in the strong antibacterial activity.

Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy.

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.