Effects of ethyl-esterization, chain-lengths, unsaturation degrees, and hyperthermia on carcinostatic effect of omega-hydroxylated fatty acids

Aim: To evaluate promotive effect of hyperthermia on the carcinostatic activity of synthesized omega-hydroxy fatty acids (wHFAs) and their ethylesters agaist Ehrlich ascites tumor (EAT) cells. Methods: EAT cells were cultured with either wHFAs or their ethylester derivatives in a water bath at either 37 °C or 42 °C for 30 min, followed by incubation in a CO2 incubator for 20 or 72 h. Mitochondrial dehydrogenase-based WST-1 assay and trypan blue dye exclusion assay were then conducted after incubation. Morphological changes were observed by scanning electron microscopy (SEM). Results: Omega-HFA having a saturated 16-carbon straight-chain (wH16:0) was the most carcinostatic (at 37 °C – viability level: 60.0%; at 42 °C – 49.6% (WST-1)) among saturated and unsaturated wHFAs with 12, 15 or 16 carbon atoms, when administrated to EAT cells at 100 µM for 20 h. Carcinostatic activity was markedly enhanced by ethyl-esterization of saturated fatty acids, such as wH16:0 (at 37 °C – 42.3%; at 42 °C – 11.2% , ibid) and wH15:0 (at 37 °C – 74.6%; at 42 °C – 25.3% , ibid), and their unsaturated counterparts were extremely effective only in combination with hyperthermia. Prolongation of the incubation period to 72 h at the same concentration increased appreciably their carcinostatic effect (wH16:0 ethylesther: 1.3%; wH15:0 ethylesther: 8.0%). These values were also supported by dye exclusion assay. The carcinostatic activity enhanced more markedly by hyperthermia (1.2%; 2.1%, ibid). SEM shows that wH16:0 ethylester-exposed EAT cells underwent extensive injury, such as deformation of cell structure or disappearance of microvilli. Conclusions: wH16:0 ethylester possesses high carcinostatic activity in vitro in combination with hyperthermia and may be utilized as potent anticancer therapeutic agent.Цель: проанализировать усиливающий эффект гипертермии на канцеростатическую активность синтезированных омегагидроксилированных жирных кислот (HFAs) и их этиловых эфиров по отноению к клеткам асцитной опухоли рлиха (EAT). Методы: клетки EAT инкубировали с HFAs или их этилэфирными производными на водной ане при 37 ° или 42 ° в течение 30 мин с дальнейим культивированием в 2 инкубаторе на протяжении 20 или 72 ч, после чего анализировали жизнеспособность клеток методами анализа WST-1, основанного на активности митохондриальных дегидрогеназ, и по включению трипанового синего. Морфологические изменения клеток определяли с использованием сканирующей электронной микроскопии. Результаты: при культивации клеток EAT в присутствии 100 M соединений в течение 20 ч омега-HFA с насыщенной 16-углеродной прямой цепью (H16:0) проявляли наиболее выраженный канцеростатический эффект (при 37 ° уровень жизнеспосоности составил 60,0%; при 42 ° 49,6% (WST-1)) по сравнению с таковым насыщенных и ненасыщенных HFAs, содержащих 12, 15 или 16 атомов углерода. анцеростатическая активность значительно возрастала при этилэтерификации насыщенных жирных кислот, таких как H16:0 (при 37 ° 42,3%; при 42 ° 11,2%, ibid) и H15:0 (при 37 ° 74,6%; при 42 ° 25,3% , ibid), в то время как производные ненасыщенных кислот были высокоэффективны только в комбинации с гипертермией. Увеличение периода инкубации клеток до 72 ч при той же концентрации веществ приводило к значительному увеличению их канцеростатического действия (этиловый эфир H16:0 1,3%; этиловый эфир H15:0 ethylesther 8,0%), подтвержденного данными окраски трипановым синим. рименение гипертермии также усиливало канцеростатическое действие соединений (1,2%; 2,1%, ibid). Результаты исследования методом SEM показали, что клетки EAT, инкубированные с этиловым эфиром H16:0, разруаются с нарушением клеточной структуры и исчезновением микроволокон. Выводы: в комбинации с гипертермией этиловый эфир H16:0 про ет высокую канцеростатическую активность in vitro, что говорит о возможности применения соединения в терапии опухолевых заболеваний

The GAPS Experiment to Search for Dark Matter using Low-energy Antimatter

The GAPS experiment is designed to carry out a sensitive dark matter search by measuring low-energy cosmic ray antideuterons and antiprotons. GAPS will provide a new avenue to access a wide range of dark matter models and masses that is complementary to direct detection techniques, collider experiments and other indirect detection techniques. Well-motivated theories beyond the Standard Model contain viable dark matter candidates which could lead to a detectable signal of antideuterons resulting from the annihilation or decay of dark matter particles. The dark matter contribution to the antideuteron flux is believed to be especially large at low energies (E < 1 GeV), where the predicted flux from conventional astrophysical sources (i.e. from secondary interactions of cosmic rays) is very low. The GAPS low-energy antiproton search will provide stringent constraints on less than 10 GeV dark matter, will provide the best limits on primordial black hole evaporation on Galactic length scales, and will explore new discovery space in cosmic ray physics. Unlike other antimatter search experiments such as BESS and AMS that use magnetic spectrometers, GAPS detects antideuterons and antiprotons using an exotic atom technique. This technique, and its unique event topology, will give GAPS a nearly background-free detection capability that is critical in a rare-event search. GAPS is designed to carry out its science program using long-duration balloon flights in Antarctica. A prototype instrument was successfully flown from Taiki, Japan in 2012. GAPS has now been approved by NASA to proceed towards the full science instrument, with the possibility of a first long-duration balloon flight in late 2020. Here we motivate low-energy cosmic ray antimatter searches and discuss the current status of the GAPS experiment and the design of the payload.Comment: 8 pags, 3 figures, Proc. 35th International Cosmic Ray Conference (ICRC 2017), Busan, Kore

Observation by an Air-Shower Array in Tibet of the Multi-TeV Cosmic-Ray Anisotropy due to Terrestrial Orbital Motion Around the Sun

We report on the solar diurnal variation of the galactic cosmic-ray intensity observed by the Tibet III air shower array during the period from 1999 to 2003. In the higher-energy event samples (12 TeV and 6.2 TeV), the variations are fairly consistent with the Compton-Getting anisotropy due to the terrestrial orbital motion around the sun, while the variation in the lower-energy event sample (4.0 TeV) is inconsistent with this anisotropy. This suggests an additional anisotropy superposed at the multi-TeV energies, e.g. the solar modulation effect. This is the highest-precision measurement of the Compton-Getting anisotropy ever made.Comment: 4 pages, 2 figures, includes .bbl fil

Large-Scale Sidereal Anisotropy of Galactic Cosmic-Ray Intensity Observed by the Tibet Air Shower Array

We present the large-scale sidereal anisotropy ofgalactic cosmic-ray intensity in the multi-TeV region observed with the Tibet-IIIair shower array during the period from 1999 through 2003. The sidereal daily variation of cosmic rays observed in this experiment shows an excess of relative intensity around $4\sim7$ hours local sidereal time, as well as a deficit around 12 hours local sidereal time. While the amplitude of the excess is not significant when averaged over all declinations, the excess in individual declinaton bands becomes larger and clearer as the viewing direction moves toward the south. The maximum phase of the excess intensity changes from $\sim$7 at the northern hemisphere to $\sim$4 hours at the equatorial region. We also show that both the amplitude and the phase of the first harmonic vector of the daily variation are remarkably independent of primary energy in the multi-TeV region. This is the first result determining the energy and declination dependences of the full 24-hour profiles of the sidereal daily variation in the multi-TeV region with a single air shower experiment.Comment: 13 pages, 3 figures, 1 table. Accepted for publication in ApJ

The influence of intergranular interaction on the magnetization of the ensemble of oriented Stoner-Wohlfarth nanoparticles

We consider the influence of interparticle interaction on the magnetization reversal in the oriented Stoner-Wohlfarth nanoparticles ensemble. To do so, we solve a kinetic equation for the relaxation of the overall ensemble magnetization to its equilibrium value in some effective mean field. Latter field consists of external magnetic field and interaction mean field proportional to the instantaneous value of above magnetization. We show that the interparticle interaction influences the temperature dependence of a coercive field. This influence manifests itself in the noticeable coercivity at $T>T_{b}$ ($T_{b}$ is so-called blocking temperature). The above interaction can also lead to a formation of the "superferromagnetic" state with correlated directions of particle magnetic moments at $T>T_{b}$. This state possesses coercivity if the overall magnetization has a component directed along the easy axis of each particle. We have shown that the coercive field in the "superferromagnetic" state does not depend on measuring time. This time influences both $T_{b}$ and the temperature dependence of coercive field at $T<T_{b}$. We corroborate our theoretical results by measurements on nanogranular films (CoFeB)$_{x}$-(SiO$_{2}$)$_{1-x}$ with concentration of ferromagnetic particles close, but below percolation threshold