3D visualization of extracellular vesicle uptake by endothelial cells

Abstract Background Extracellular vesicles are small vesicles that contain cytoplasmic and membrane components from their paternal cells. They enter target cells through uptake to transfer their biological cargo. In this study, we investigated the process of endothelial EV internalization and created a 3D visualization of their intracellular distribution. Methods and results Two immortalized endothelial cell lines that express h-TERT (human telomerase) were used for EV release: microvascular TIME and macrovascular HUVEC. EVs were isolated from the cell culture medium via differential centrifugation and used for the uptake experiments. The size distribution of the EVs was measured using TRPS technology on a qNano instrument. Internalization of EVs was observed using a Zeiss LSM 710 confocal laser microscope after staining of the EVs with PKH26. EVs were observed intracellularly and distributed in the perinuclear region of the target cells. The distribution patterns were similar in both cell lines. Conclusion The perinuclear localization of the internalized EVs shows their biological stability after their uptake to the endothelial cells. The 3D visualization allows the determination of a more accurate location of EVs relative to the donor cell nucleus

Data regarding particle size distribution, thermal properties and gaseous phase hydration of co-milled solid dispersions composed of tadalafil and Soluplus

A mechanical activation of the solid particles upon high-energy ball milling may considerably change the physicochemical properties of pharmaceutical compounds, including the morphology, particle size distribution, thermal properties, and surface interactions with water vapour upon gaseous phase hydration. Assessment of these changes is crucial for optimizing the manufacturing process of enabling drug products. In this article, we provide a detailed characterization of binary co-milled solid dispersions composed of tadalafil and Soluplus using a laser diffraction method, differential scanning calorimetry (DSC), gravimetric measurements and solid state (1)H- NMR spectroscopy. The data presented in this article is directly related to our previously published research article. They complement information on the impact that both formulation and process variables may have on the properties of these binary powder formulations

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

The hydrating properties of tadalafil formulations in the matrix polymer Soluplus

W pracy przedstawiono badania hydratacji próbek tadalafil dla poprawy rozpuszczalności leku umieszczonych w osnowie polimerowej Soluplus. Pomiary wykonano przy użyciu metod spektroskopii magnetycznego rezonansu jądrowego. Pomiary kinetyki hydratacji mieszanin tadalafil:Soluplus pozwoliły wyróżnić trzy frakcje wody związanej.The paper presents the study of hydration samples tadalafil to improve the solubility of the drug contained in the polymer matrix Soluplus. Measurements were made using the methods of nuclear magnetic resonance spectroscopy. Measurements of the kinetics of hydration mixtures tadalafil: Soluplus allowed divided into three fractions of bound water. Hydration kinetics, sorption isotherm, and proton free induction decays are measured for tadalafil formulations in the matrix polymer Soluplus hydrated from gaseous phase. Very tightly, tightly and loosely bound water fraction are distinguished

The study of relaxation properties of modern contrast agents for magnetic resonance imaging

Obiektem badań w mojej pracy były nanokapsułki do transportu leków z wbudowanymi w otoczkę superparamagnetycznymi tlenkami żelaza, w celu zapewnienia wizualizacji ich dystrybucji metodą obrazowania magnetyczno-rezonansowego. W zakresie moich badań było wyznaczenie czasów relaksacji T1 i T2 nanokapsułek z pojedyncza i podwójną warstwą tlenków żelaza wbudowaną w otoczkę, oraz ocena uzyskanego kontrastu przy zastosowaniu kilku metod obrazowania MR.The object of research in my work were nanocapsules for drug delivery with built-in shell superparamagnetic with iron oxides, in order to visualize the distribution by magnetic resonance imaging. In terms of my research was to determine the relaxation times T1 and T2 nanocapsules with a single and a double layer of iron oxide shell built-in, and the assessment of the contrast obtained using several methods of MR imaging

How rotational speed of planetary ball mill and polymer load influence the performance and water vapor sorption in solid dispersions composed of tadalafil and soluplus

The presence of residual water may deteriorate the performance of amorphous solid dispersions prepared by ball milling, affecting molecular mobility, crystallinity, particle size and finally, the drug dissolution rate. As the stability of these metastable systems depend on both formulation and process variables, the aim of this study was to assess for the first time, the impact that the polymer load and the rotational speed applied upon high energy ball milling could have on the performance of binary co-milled solid dispersions composed of tadalafil (a hydrophobic crystalline drug) and Soluplus (an amphiphilic, hygroscopic amorphous polymer). Each of these variables was tested at three levels. Scanning electron microscopy, laser diffraction and X-ray powder diffraction were used to analyze morphology, particle size distribution and crystallinity of ball milled formulations respectively. Dissolution studies were also carried out. Advanced tools of applied physics, namely solid state 1H NMR and relaxometry were used to assess the structure and water mobility upon gaseous phase hydration on storage. It was shown that both tested variables determined the particle size of the formulation. When the rotational speed of 400 rpm was used, all solid dispersion were XRD-amorphous, but to ensure the immediate release of tadalafil its micellar solubilization in Soluplus was necessary. While the formulation was exposed to water vapor, the hydration level increased with an increasing polymer load as well. Hence, the rotational speed governed the space available for the adsorption of water molecules and their organization in a monolayer or multilayers. Such behavior may have impact on the kinetics of the amorphous drug recrystallization, and finally deteriorate its dissolution