Tumor microenvironment: the formation of the immune profile

Tumor microenvironment (TME) is formed as a result of interaction and cross-linking between the tumor cell and different types of surrounding cells. Recent studies have shown that the tumor reprograms the microenvironment so that TME promotes the development of primary tumors, their metastasis and becomes an important regulator of oncogenesis. Under the influence of the tumor, the immune profile in the TME undergoes significant changes, “editing". An immunosuppressive network is formed, which suppresses the activity of the main effector of cellular immunity — T lymphocytes. T cells in TMA are in a state of anergy and exhaustion. T cells in TME are characterized by increased expression of inhibitory receptors, decreased secretion of cytokines and cytolytic activity. Blocking inhibitory receptors with specific antibodies can lead to the restoration of the functions of exausted T cells. Therefore, the restoration of the functional activity of T lymphocytes is one of the important strategies in cancer immunotherapy. The formation of the immune profile is influenced by genetic aberrations accumulating in the tumor. They play an important role in creating a specific, characteristic only for this tumor immune environment in the TME. Genetic changes in tumor cells lead to phenotypic and functional rearrangements of lymphocytes, which allows the tumor to escape the reaction of immune cells. Since many tumors occur after prolonged inflammation or exhibit characteristics of chronic inflammation as they progress, inflammation is considered an important factor in the formation of immune profile in TME. Immune infiltrates from different human tumors associated with inflammation may contain valuable prognostic and pathophysiological information. Macrophages in the TME now began to be regarded as descriptive marker and as a therapeutic target. One of the main mechanisms by which tumor cells reprogram surrounding cells is the release of exosomes — small vesicles that carry and deliver proteins and nucleic acids to other cells. When exosomal cargo is absorbed, molecular, transcriptional and translational changes occur in the recipient non-tumor cells in the TME. Therefore, tumor exosomes are an effective means by which the functions of immune cells in TME are purposefully changed. Thus, along with individual molecular and genomic testing of the tumor, attention should be paid to a deeper analysis of the immune profile of TME. It is a large resource of biomarkers and targets for immunotherapy

ИССЛЕДОВАНИЕ ПРОБЛЕМ БЕЗОПАСНОСТИ ИСПОЛЬЗОВАНИЯ КОРОТКИХ ССЫЛОК

В работе рассмотрены сферы применения коротких ссылок, указаны их преимущества и недостатки. Описаны возможные уязвимости и атаки, а также методы защиты от них. Проанализирован общий уровень безопасности использования коротких ссылок

Aerodynamic investigations of ventilated brake discs.

The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry

The Effects of Fourth Generation on the double Lepton Polarization in B \rar K \ell^+ \ell^- decay

This study investigates the influence of the fourth generation quarks on the double lepton polarizations in B \rar K \ell^+ \ell^- decay. Taking |V_{t's}V_{t'b}|\sim \{0.01-0.03\} with phase about 100^\circ, which is consistent with the b\to s\ell^+\ell^- rate and the B_s mixing parameter Delta m_{B_s}$, we obtain that the double lepton(muon and tau) polarizations are quite sensitive to the existence of fourth generation. It can serve as a good tool to search for new physics effects, precisely, to indirect search for the fourth generation quarks(t', b').Comment: 30 pages, 27 figure