Cold Medium Research Articles

Absorption by Spinning Dust: A Contaminant for High-redshift 21 cm Observations

Abstract Spinning dust grains in front of the bright Galactic synchrotron background can produce a weak absorption signal that could affect measurements of high-redshift 21 cm absorption. At frequencies near 80 MHz where the Experiment to Detect the Global EoR Signature (EDGES) has reported 21 cm absorption at z ≈ 17 , absorption could be produced by interstellar nanoparticles with radii a ≈ 50 Å in the cold interstellar medium (ISM), with rotational temperature T ≈ 50 K. Atmospheric aerosols could contribute additional absorption. The strength of the absorption depends on the abundance of such grains and on their dipole moments, which are uncertain. The breadth of the absorption spectrum of spinning dust limits its possible impact on measurement of a relatively narrow 21 cm absorption feature.

Iron and Silicate Dust Growth in the Galactic Interstellar Medium: Clues from Element Depletions

Abstract The interstellar abundances of refractory elements indicate a substantial depletion from the gas phase, which increases with gas density. Our recent model of dust evolution, based on hydrodynamic simulations of the life cycle of giant molecular clouds (GMCs), proves that the observed trend for [Sigas/H] is driven by a combination of dust growth by accretion in the cold diffuse interstellar medium (ISM) and efficient destruction by supernova (SN) shocks. With an analytic model of dust evolution, we demonstrate that even with optimistic assumptions for the dust input from stars and without destruction of grains by SNe it is impossible to match the observed [Sigas/H]–n H relation without growth in the ISM. We extend the framework developed in our previous work for silicates to include the evolution of iron grains and address a long-standing conundrum: “Where is the interstellar iron?” Much higher depletion of Fe in the warm neutral medium compared to Si is reproduced by the models, in which a large fraction of interstellar iron (70%) is locked as inclusions in silicate grains, where it is protected from efficient sputtering by SN shocks. The slope of the observed [Fegas/H]–n H relation is reproduced if the remaining depleted iron resides in a population of metallic iron nanoparticles with sizes in the range of 1–10 nm. Enhanced collision rates due to the Coulomb focusing are important for both silicate and iron dust models to match the slopes of the observed depletion–density relations and the magnitudes of depletion at high gas density.

Cooling time of porous asphalt pavement affecting compaction process due to various raining condition

While bright sunshine and warm temperatures make for the best paving weather, construction projects can get a bit rough in adverse weather conditions. In this case, porous asphalt is used on paving. Light sprinkles can usually be handled without any serious problems. Moderate rainfall events, on the other hand, will generally require the paving project to be postponed. Steady downpours will cool the porous asphalt mix and make proper compaction extremely difficult to obtain. For the viability of the project, contractors will always wait until the sky clears up. According to the JKR Specification 4(Clause 4.2.6.4), it clearly states that no pavement work should be done during rain. The rain is a cold medium where it will actually cools down everything that make contact with the water. Whereas, the mix porous asphalt (PA) is a hot medium. When these two elements combined, the surface and the PA will harden at a stage where it will not be well compacted. This will cause problems in the future. The test is conducted by pouring water onto the pavement(through raining simulation).Since the rain intensity can be determined by the size of the rain drops, the difference in the shower hole size is good enough to create different rain intensities to predict the PA cooling rate when it makes contact with water. These two variables will work as a comparison in this study between raining and no rain condition. As a result, whenever the water make a contact with the PA, the rates of cooling drops 98% from the normal rates of cooling of PA (without rain)giving the Time Available for Compaction (TAC) to be less than 60 seconds. This study may be a knowledge on how the rates of cooling work if the PA make contact with water. It can also be used as future reference on the study of cooling rates of porous pavement during raining condition.

Increased Soluble Protein Oligomer in Sepsis is Associated with the Induction of Pro‐inflammatory Signal Transduction in Intra‐renal Arteries

IntroductionSepsis is a profoundly morbid and life‐threatening condition affecting every organ in the body. Acute kidney injury (AKI) is a frequent and serious complication of sepsis, and accounts for greater than 50% of cases in the critically ill. Sepsis‐associated AKI is known to develop even in the absence of hemodynamic alterations suggesting contributions from unique inflammatory and immune mechanisms. There has been growing interest in the role of prefibrillar, soluble protein oligomers (SPO) as being primarily responsible for the observed toxicity in a number of age‐related degenerative diseases. SPOs have been shown to activate a variety of pattern recognition receptors (PRRs) leading to pro‐inflammatory signal transduction in these conditions. Endoplasmic reticulum stress in the septic response has been shown activate the unfolded protein response and induce apoptosis. Based on these observations, we hypothesize that the cellular insult in sepsis is sufficiently severe to overwhelm proteostasis mechanisms and lead to the accumulation of SPO in multiple systems, and that SPOs represent damage‐associated molecular patterns (DAMPs) which contribute to the inflammatory state and loss of cellular and tissue integrity observed in sepsis.MethodsMale C57BL/6 mice (age 3–5 months) underwent cecal ligation and puncture (CLP) as a model of sepsis, and sham surgery as a control. Dot blots were performed using A11 anti‐oligomer antibody and secondary donkey anti‐rabbit peroxidase‐linked antibody. For toxicity studies, soluble oligomer was prepared by dissolving amyloid‐β1–42 peptide in hexaflouro‐2‐propanol (HFIP) that was allowed to evaporate before being diluted in cold phenol‐free F12 medium as previously described. Oligomer formation was confirmed by dot blot. Mouse heart and intra‐renal arteries were then incubated in 10‐μM SPO solution for 4 hours, and western blot was performed for p‐ERK and COX‐1 expression.ResultsSoluble oligomer is increased in the heart and intrarenal arteries of CLP mice (1.8 and 1.4 fold vs. control respectively, p < 0.05). (Figure 1) Exposure of intrarenal arteries to 10‐μM soluble oligomer is associated with increased expression of pro‐inflammatory p‐ERK (2.1 fold vs control, p<0.05, Figure 2) and a tendency towards increased COX‐1 expression (p>0.05).ConclusionSepsis is associated with increased soluble protein oligomer in the heart and intra‐renal arteries. Exposure of intra‐renal arteries to SPO is associated with the increased expression of the pro‐inflammatory signaling pathway p‐ERK. These findings support the notion that elevated SPO in sepsis is involved in propagating the inflammatory cascade. The presence of soluble oligomer in the renal vasculature in sepsis and its induction of inflammatory mediators offers a compelling novel mechanism for sepsis‐associated AKI with or without extra‐renal hemodynamic compromise with the potential for specific and novel therapeutic interventions.Support or Funding InformationNIH: P01HL134604, NIH: 1K99GM118885‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dispersion of gravitational waves in cold spherical interstellar medium

We investigate the propagation of locally plane, small-amplitude, monochromatic gravitational waves (GWs) through cold compressible interstellar gas in order to provide a more accurate picture of expected waveforms for direct detection. The quasi-isothermal gas is concentrated in a spherical symmetric cloud held together by self-gravitation. Gravitational waves can be treated as linearized perturbations on the background inner Schwarzschild spacetime. The perturbed quantities lead to the field equations governing the gas dynamics and describe the interaction of gravitational waves with matter. We have shown that the transport equation of these amplitudes provides numerical solutions for the frequency-alteration. The decrease in frequency is driven by the energy dissipating process of GW–matter interactions. The decrease is significantly smaller than the magnitude of the original frequency and too small to be detectable by present second-generation and planned third-generation detectors. It exhibits a power-law relationship between original and decreased frequencies. The frequency deviation was examined particularly for the transient signal GW150914.

Plasma-stimulated medium kills TRAIL-resistant human malignant cells by promoting caspase-independent cell death via membrane potential and calcium dynamics modulation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cold plasma-stimulated medium (PSM) have been shown to exhibit tumor-selective cytotoxicity and have emerged as promising new tools for cancer treatment. However, to date, at least to the best of our knowledge, no data are available as to which substance is more potent in killing cancer cells. Thus, in this study, we systematically compared their abilities to kill human malignant cells from different origins. We found that PSM dose-dependently killed TRAIL-resistant melanoma, osteosarcoma and neuroblastoma cells. Moreover, PSM had little cytotoxicity toward osteoblasts. PSM was more potent than TRAIL in inducing caspase-3/7 activation, mitochondrial network aberration and caspase-independent cell death. We also found that PSM was more potent in inducing plasma membrane depolarization (PMD) and disrupting endoplasmic-mitochondrial Ca2+ homeostasis. Moreover, persistent PMD was caused by different membrane-depolarizing agents; the use of the anti-type II diabetes drug, glibenclamide, alone caused mitochondrial fragmentation and enhanced TRAIL-induced Ca2+ modulation, mitochondrial network abnormalities and caspase-independent cell killing. These results demonstrate that PSM has a therapeutic advantage over TRAIL owing to its greater capacity to evoke caspase-independent cell death via mitochondrial network aberration by disrupting membrane potential and Ca2+ homeostasis. These findings may provide a strong rationale for developing PSM as a novel approach for the treatment of TRAIL-resistant malignant cells.

Properties of [formula omitted], [formula omitted] and [formula omitted] heavy baryons in cold nuclear matter

The in-medium properties of the heavy spin-3/2 ΣQ⁎, ΞQ⁎ and ΩQ⁎ baryons with Q being b or c quark are investigated. The shifts in some spectroscopic parameters of these particles due to the saturated cold nuclear matter are calculated. The variations of those parameters with respect to the changes in the density of the cold nuclear medium are studied, as well. It is observed that the parameters of ΣQ⁎ baryons are considerably affected by the nuclear matter compared to the ΞQ⁎ and ΩQ⁎ particles that roughly do not see the medium. The results obtained may be used in analyses of the data to be provided by the in-medium experiments like PANDA.

ϕ Meson Measurements at RHIC with the PHENIX Detector

The measurement of ϕ mesons provides key information on the phase of the hot and dense medium created in the relativistic heavy ion collisions. It has a relatively small hadronic interaction cross section and is sensitive to the increase of strangeness (strangeness enhancement), a phenomenon associated with soft particles in bulk matter. Measurements in the dilepton channels are especially interesting since leptons interact only electromagnetically, thus carrying the information from their production phase directly to the detector. Measurements in different nucleus-nucleus collisions allow us to perform a systematic study of the nuclear medium effects on ϕ meson production. The PHENIX detector provides the capabilities to measure the ϕ meson production in a wide range of transverse momentum and rapidity to study these effects. In this proceeding, we present measurements of the ϕ mesons in a variety of collision systems at [see formula in PDF] = 200 GeV. In case of small systems, the data are compared with AMPT calculations to study the various cold nuclear medium effects involved in ϕ meson production.

On the gas-phase formation of the HCO- anion: accurate quantum study of the H- + CO radiative association and HCO radiative electron attachment.

The hydrogen anion has never been observed in the interstellar medium, but it is most likely present in some interstellar regions. Since direct detection appears especially difficult, improving the knowledge of the astrochemical processes involving this anion should be valuable in defining a way of indirect detection. We present the first study of the radiative association of H- and CO to form the HCO- anion within a quantum time-independent approach. We use a state-of-the-art potential energy surface which has been calculated for the present study. The calculated radiative association rate coefficient is monotonically decreasing from 6 × 10-16 to 5 × 10-19 cm3 per molecule per s across the 0.01-1000 K temperature range. At the typical temperature of the cold interstellar medium, ∼10 K, the radiative association rate is ∼2 × 10-17 cm3 per molecule per s. On the other hand, the plane wave approximation is used to calculate the HCO radiative electron attachment rate coefficient. It is found to be almost constant and also equal to 2 × 10-17 cm3 per molecule per s. Setting aside the question of the abundances of the reactants of both processes, these results demonstrate that among the two gas-phase modes of production of the HCO- anion in cold interstellar medium considered in this study, the H- + CO radiative association is dominating below 10 K while the radiative electron attachment rate is larger above 10 K.

Atomic fountain frequency standard: principle and development

The principle and development of fountain frequency standard are introduced in this paper. Fountain frequency standard is an atomic clock technology developed in recent 20 years. It is based on laser cooling technology, and realizes the trapping and projection of the cold atom medium with laser cooling technology. In the process of launching upward and falling back, the cold atom medium first completes the preparation of atomic state, then passes through the microwave cavity twice to achieve the Ramsey interaction; between the two interactions it undergoes free evolution, and finally the Ramsey interference fringes are obtained by detecting the atomic interference probability with the two-level fluorescence detection method in the detection region, and the frequency is locked with a line width of the central fringe being about 1 Hz. The stability and uncertainty of the frequency are two important indexes of the fountain frequency standard. The factors influencing the stability of the fountain clock frequency mainly are quantum projection noise and electronic noise. At present, the short term stability of the fountain clock is (10-13-10-14)τ-1/2, and the long term stability is (10-16-10-17). The frequency uncertainty of the fountain frequency standard is mainly influenced by the two-order Zeeman frequency shift, the blackbody radiation frequency shift, the cold atom collisional frequency shift, and the frequency shift relating to the microwave. The uncertainty of the fountain clock is around 10-16 currently. As a reference frequency standard, the working media of the fountain clock mainly are 133Cs and 87Rb. All international metrology institutions have been developing the fountain frequency standard, and it plays a more and more important role in establishing the coordinated universal time and the calibration of the international atomic time. In addition, the fountain frequency standards are also used to study high-precision time-frequency reference and time comparison chain, and verify basic physical theories.

No Sign of Strong Molecular Gas Outflow in an Infrared-bright Dust-obscured Galaxy with Strong Ionized-gas Outflow

Abstract We report the discovery of an infrared (IR)-bright dust-obscured galaxy (DOG) that shows a strong ionized-gas outflow but no significant molecular gas outflow. Based on detailed analysis of their optical spectra, we found some peculiar IR-bright DOGs that show strong ionized-gas outflow ([O iii] λ5007) from the central active galactic nucleus (AGN). For one of these DOGs (WISE J102905.90+050132.4) at z spec = 0.493, we performed follow-up observations using ALMA to investigate their CO molecular gas properties. As a result, we successfully detected 12CO(J = 2–1) and 12CO(J = 4–3) lines and the continuum of this DOG. The intensity-weighted velocity map of both lines shows a gradient, and the line profile of those CO lines is well-fitted by a single narrow Gaussian, meaning that this DOG has no sign of strong molecular gas outflow. The IR luminosity of this object is log (L IR/L ☉) = 12.40, which is classified as an ultraluminous IR galaxy (ULIRG). We found that (i) the stellar mass and star formation rate relation and (ii) the CO luminosity and far-IR luminosity relation are consistent with those of typical ULIRGs at similar redshifts. These results indicate that the molecular gas properties of this DOG are normal despite the fact that its optical spectrum shows a powerful AGN outflow. We conclude that a powerful ionized-gas outflow caused by the AGN does not necessarily affect the cold interstellar medium in the host galaxy, at least for this DOG.

Nonlinear Spectroscopy of Alkali Atoms in Cold Medium of Astrophysical Relevance

The time-dependent population dynamics of hyperfine (HF) sublevels of n 2 p 3 / 2 atomic states upon laser excitation in a cold medium of alkali atoms is examined. We demonstrate some peculiarities of the absorption HF multiplet formation in D2-line resulting from a long interaction time (∼200 μ s) interaction between light and Na ( n = 3 ) and Cs ( n = 6 ) atoms in a cold and slow sub-thermal ( T ∼ 1 K) beam. We analytically describe a number of D2-line-shape effects that are of interest in spectroscopic studies of cold dusty white dwarfs: broadening by optical pumping, intensity redistribution within components of D2-line HF multiplet for partially closed transitions and asymmetry of absorption lines induced by AC Stark shifts for cyclic transitions.

Evolution of Molecular Clouds in the Superwind Galaxy NGC 1808 Probed by ALMA Observations

Abstract ALMA imaging of the cold molecular medium in the nearby starburst galaxy NGC 1808 is presented. The observations reveal the distribution of molecular gas, traced by 12CO (1–0) and 12CO (3–2), and continuum (93 and 350 GHz) across the central 1 kpc starburst region at a high resolution of . A molecular gas torus (radius ∼ 30 pc) is discovered in the circumnuclear disk (CND; central 100 pc), with a high CO (3–2)/CO (1–0) ratio of ∼1, surrounded by massive (106– ) clouds with high star formation efficiency ( yr−1), molecular spiral arms, and a 500 pc pseudo-ring. The CND harbors a continuum core and molecular gas exhibiting peculiar motion. The new data confirm the line splitting along the minor galactic axis, interpreted as a nuclear gas outflow with average velocity ∼180 km s−1, and show evidence of a velocity gradient of km s−1 pc−1 along the axis. In addition, supershells expanding from the 500 pc ring with maximum velocities of ∼75 km s−1 are revealed. The distribution and CO luminosities of molecular clouds in the central 1 kpc starburst region indicate an evolutionary sequence, from gas accretion onto the 500 pc ring from the large-scale bar to enhanced star formation in the ring, and outflow as feedback.

Safer and healthier reduced nitrites turkey meat sausages using lyophilized Cystoseira barbata seaweed extract.

Background Nitrite salts are still common additives in the meat industry. The present study provides a first approach on the employment of the lyophilized aqueous extract (WE) of the Tunisian seaweed Cystoseira barbata for the quality enhancement of turkey meat sausage. Methods WE was supplemented as a natural antioxidant agent to investigate its effectiveness in delaying lipid oxidation turkey meat sausages containing reduced amounts of sodium nitrites. Results On storage day 5, all concentrations of WE (0.01-0.4 %) reduced the meat lipid oxidation by approximately 36 %, as compared to the negative control containing only 80 mg/kg of meat of sodium nitrites as antioxidant. It was noted that within 15 days of refrigerated storage, a meat system containing 80 mg/kg of meat of sodium nitrites and 0.02 % and 0.04 % of WE had similar Thiobarbituric Acid Reactive Substances (TBARS) levels (19±1.32 and 17±1.12 µmol/kg of meat, respectively), which were comparable to the positive control containing sodium nitrites (150 mg/kg of meat) and 0.045 % vitamin C (18.46±1.27 µmol/kg of meat). In-depth, the metabolomic profiling using gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-quadripole-time-of-flight-mass spectrometry (LC-QTOF-MS) analyses of the Tunisian seaweed C. barbata solvent extracts showed that the main active compounds were phenolic compounds, fatty acids and sterols. Conclusions Overall, the cold medium containing C. barbata lyophilized aqueous extrac, with strong antioxidant activity and antihypertensive properties, may open the way to the development of a natural quality enhancement strategy for new functional and ever healthier reduced nitrites meat sausages based on algae.

Electro-gravity spin density waves

It is known that some string models predict that strong bursts of gravitational radiation which should be detectable by LIGO, VIRGO and LISA detectors are accompanied by cosmologic gamma-ray bursts (GRBs). GRBs of low-energy gamma ray are associated with core-collapse supernovae (SN). However, measurements of the X-ray afterglow of very intense GRBs (allow a critical test of GRB theories) disagree with that predicted by widely accepted fireball internal–external shocks models of GRBs. It is also known that in a system of a large number of fermions, pairs of gravitational interaction occur on spontaneous breaking of the vacuum spatial symmetry, accompanied by gravitational mass defect. In another side, the space rays generation mechanism on a method of direct transformation of intergalactic gamma-rays to the proton current on spin shock-waves ensures precise agreement between generated proton currents (spin shock waves theory) with the angular distribution data of Galactic gamma-rays as well as for the individual pulses of gamma-/X-ray bursts. There is a precise confirmation of the generated currents (theory) with the burst radiation data characterized by the standard deviation of [Formula: see text] in intensity in relative units within the sensitivity of the equipment. Thus, it was found that the spin angular momentum conservation law (equation of dynamics of spin shock waves) in the X-ray/gamma ranges is fulfilled exactly in real time. The nature of gamma bursts is largely determined by the influence of powerful external sources. The angular distributions anisotropy of Galactic gamma rays and pulsars are determined by the paradoxes way, so this can only take place under conditions of the isotropy of space–time. In this regard, promising gravity in a Finsler space can have the selected direction in flat Minkowski space metric with torsion as in the Einstein–Cartan theory. Considering the induction of torsion in conformal transformations of tetrades (N-ades in arbitrary dimension N) under the Conformal Gauge Theory of Gravity (CGTG), here is considered an exact cosmological solution with Friedman’s asymptotic in the form of conformal flat Fock’s metrics at large times, describing the stage of decay on a cold dust-like medium of do-not-interacting-among-themselves particles and a light-like isotropic radiation. It is shown that at high times, indeed, the process of enlarging the space–time in the model metrics Friedman conformal is equivalent to Minkowski space with a gradient torsion trace in the CGTG Newtonian limit, accompanied by a polarization effect separation of electric charges induced by an electric field [Formula: see text] is manifested in the formation of plasma-like medium with a zero complete electric charge, that in the later stages of evolution is identical to the Fock’s model of a cold dust-like medium of do-not-interacting-among-themselves particles moving here with the same speed. The trace of torsion on the CGTG formula is freezing into an electromagnetic field spin tensor trace density and [Formula: see text] defined inside a spherical surface, moving at the speed of light, on which experiencing a gap. Therefore, this decision takes the form of an electro-gravity spin density wave, as performed in kinematic and dynamic close connection conditions for theorems on spin shock waves with spin flip at the front of the wave, moving at the speed of light in a vacuum. The theoretical dependence of electro-gravity wave energy output from the size of the emitting object is received. When applied to GRBs, this can give a new mechanism of nonthermal gamma rays production.

Goos–Hänchen Shift from Cold and Hot Atomic Media Using Kerr Nonlinearity

We study and examine the Goos–Hanchen shifts of a propagating probe light field in a four-level tripodtype cold and hot atomic medium. The behavior of Goos–Hanchen shifts is studied in reflection and transmission beams in the presence of the coherent Kerr effect and the Doppler broadening effect. We observe that these shifts can be controlled by the relative propagation direction of the control field to that of the probe field.

Comparing the thermodynamic potential of alternative liquid metal oxides for the storage of solar thermal energy

The relative potential of liquid multivalent metal oxides for the storage of thermal energy as sensible, latent and/or thermochemical storage energy in a liquid chemical looping thermal enerrgy storage (LCL-TES) is reported. This LCL-TES cycle comprises a reduction reactor, an oxidation reactor, two reservoirs for storing the hot and cold medium and a heat recovery unit. The materials were assessed on the basis of their melting temperature, Gibbs free energy, reaction temperature and thermal storage capacity. Ellingham diagrams were used to identify regimes with a potential for application in a LCL-TES, while phase diagrams were used to identify processes which combine sensible, latent and thermochemical heat storage. Based on these criteria, the oxide of CuO/Cu2O was found to have the greatest thermodynamic potential for use in a LCL-TES system with a total enthalpy of 404.67kJ/mol for thermal storage. However, the high temperature of ∼1200°C and corrosive nature of molten copper and its oxides will make this cycle challenging to implement. Lead, on the other hand has a lower total enthalpy of 250.09kJ/mol, but is molten at lower temperatures.

Hot rolled and cold rolled medium manganese steel: Mechanical properties and microstructure

The current work aims at obtaining optimum amount of austenite after processing of a medium manganese steel in order to invoke partial twinning induced plasticity (TWIP) mechanism during deformation and to maximise elongation. Steel chemistry was optimised using thermodynamic calculations and the same was processed in different ways which includes continuous cooling from single phase austenitic region, quenching + austenite reverted transformation (ART) annealing and austenite reverted transformation (ART) annealing. DICTRA and Thermo-Calc simulation was done to understand the austenite to ferrite transformation kinetics during continuous cooling and the mode of equilibrium that is operative. The study suggests that quenching + austenite reverted transformation (ART) annealing is the ideal approach for processing this material in order to get the desired microstructure and properties. Thermo-Calc and Koistinen and Marburger's (KM) equation was coupled to estimate the fraction of austenite to be retained after isothermal holding at different intercritical temperatures and the optimum temperature found was used for annealing this steel. Microstructural characterization along with tensile test was done to ascertain the effect of processing route, initial microstructure on the mechanical properties. It was found that the morphology of austenite was greatly affected by the initial microstructure of the steel. Mechanical properties obtained after cold rolling (CR) and austenite reverted transformation (ART) annealing was found to be superior to that of hot rolling (HR) and austenite reverted transformation (ART) annealing. The difference in mechanical properties was correlated with the austenite morphology and the final microstructure.

Development of an assay for cellular efflux of pharmaceutically active agents and its relevance to understanding drug interactions.

Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs, and understanding how these drugs interact is of the utmost importance. The pharmacokinetics of busulfan, melphalan, and cyclophosphamide, drugs commonly used for HSCT, are known to be affected by a variety of other drugs with differing molecular structures. We hypothesized that these structurally unrelated drugs affect the transport of DNA-alkylating agents. To test this hypothesis, we developed a flow cytometry assay that used 5-carboxyfluorescein diacetate acetoxymethyl ester, which is cleaved by nonspecific intracellular esterases to 5-carboxyfluorescein (5-CF), a fluorescent ligand for the drug transporter MRP1. A decreased 5-CF efflux in the presence of a test compound suggests competitive inhibition. We demonstrated that chlorambucil, 4-hydroperoxycyclophosphamide, ketoconazole, ethacrynic acid, everolimus, and sirolimus strongly inhibited 5-CF efflux in lymphoma and leukemia cell lines. The efflux of these drugs partially depends on the glutathione (GSH) level, and their cytotoxicity is synergistic with inhibited GSH synthesis. This is consistent with the hypothesis that their GSH-conjugated products are ligands of a common cellular drug transporter. Our results may explain clinical observations on the effects of various drugs on the pharmacokinetics and pharmacodynamics of alkylating agents, and the assay may be used to deduce interaction mechanisms of drugs transported by a common system.

Azimuthal correlations of D-mesons in p+p and p+Pb collisions at LHC energies

We study the correlations of D mesons produced in $p$+$p$ and $p$+Pb collisions. These are found to be sensitive to the effects of the cold nuclear medium and the transverse momentum ($p_T$) regions we are looking into. In order to put this on a quantitative footing, as a first step we analyse the azimuthal correlations of D meson-charged hadron(Dh), and then predict the same for D meson -anti D meson ($D\overline{D}$) pairs in $p$+$p$ and $p$+Pb collisions with strong coupling at leading order $\cal{O}$($\alpha_{s}^{2}$) and next to leading order $\cal{O}$($\alpha_{s}^{3}$) which includes space-time evolution (in both systems), as well cold nuclear matter effects (in $p$+Pb). This also sets the stage and baseline for the identification and study of medium modification of azimuthal correlations in relativistic collision of heavy nuclei at the Large Hadron Collider.